Study Result

Sep 12, 2021

Good afternoon and good morning, everyone. I'm Marty Duvall, CEO of Oncopeptides, and welcome to the Oncopeptides post IMW webcast. Yesterday at the IMW meeting here in Vienna, Doctor. Frederick Schestfeld presented a late breaking abstract on the ocean dataset representing the first introduction of trial details in a peer reviewed public setting. Over the past 24 hours, We've been pleased to hear the feedback on this excellent presentation as well as the strong interest in the ocean data results. Today, you will have the opportunity to hear directly from Doctor. Schestfold and participate in a Q and A on the data and perspectives. And to present your question. There's a form in the webcast where you can type that in and we'll have the opportunity to talk about it. If you could flip the slide forward. Importantly, we will be making some forward looking statements today, so please refer to all of our submissions for appropriate balance on representations and warranties of the data as we describe it. Next slide, please. So, the format today will be that presentation of the ocean data and Doctor. Schestfeld will include a couple of additional slides. And most importantly, we will have a question and answer session with Doctor. Schestfeld and Doctor. Bacher. Then Klosbacher, our CMO, will provide a view on the OSHA data, the opportunity and regulatory update. We'll also hear about our PORT trial and those Phase 2 data results We're presented at the IMW meeting in a poster format and represent an important future expansion of mode of delivery of popaxto from a commercial perspective. And then I'll provide some closing remarks. So, we'll move into the program with Doctor. Bacher introducing Doctor. Schestfeld. Claes, thank you. Thank you, Marty. And before I hand the baton to Doctor. Chesvoldt. I would like to just make some statements beforehand on the fact that the FDA has approved pipaxto in patients who are triple class refractory and have received 4 prior lines of treatment and this was under accelerated approval. In the OCEAN study. The superior PFS meeting the primary endpoint was there. However, overall survival was in favor of pomalidomide with a hazard ratio of 1.1. Based on this, the FDA has issued a partial clinical hold and as a follow-up of that, there will be a Oncology Drug Advisory Committee meeting, in short ODEC, on the 28th October 2021. And we are, as we speak, cooperating with the FDA on the OCEAN data. Next slide, please. And now it's a pleasure to introduce Doctor. Frederic Cheswold, Head of the Myeloma Centre at Oslo University Hospital. And importantly, Doctor. Jeswald enrolled most patients in the OCEAN trial and has a vast clinical experience with melflutphen. And he is here now to provide you with an extended version of the ocean presentation. Doctor. Scheswold, the floor is yours. Thank you. Thanks for the introduction and thanks for giving me the opportunity to show this data Again, as you said, a little bit expanded. So the OCEAN study, a Phase 3 study randomized, and it's a head to head study between Melfrufindex and Komlidmidex. This is not so common in myeloma. There are some studies of course but most randomized studies our add on studies where you have a standard of care versus the same treatment plus something else. This study had just between 2 drugs and the additional dexamethasone in both of course and that gives often a bit more interesting results and we will look at that here. Next slide please. Next slide, this is by the disclosures. Next slide. So, Milleflufen is a very new type of drug, it's what we call a peptidrug conjugate that means it's a drug conjugated or bound to a peptide. This conjugates Makes the drug lipophilic. It means that it can rapidly into cells But it can also rapidly diffuse out of cells again. So what happens to prevent that is that melflufen It's hydrolyzed by aminopeptidases that are enzymes in the cells. And after it's been hydrolyzed, it releases alkylating agents like an alkylating drug and that drug is not lipophilic so that doesn't diffuse out of the cell as rapidly. And what we see with this drug is that In cells that have much of this enzyme, this aminopeptidase enzymes, A larger amount of this alkylating drug is trapped in the cells. So it means that the sort of chemotoxicity from this drug. It's mainly seen in cells that have a large amount of aminopeptidases. And the reason this This mechanism is chosen is that myeloma cells and also some other cancer cells do have a large expression of aminopeptidases. And that means that in contrary to a normal alkylator you give orally or intravenously which works sort of in the same way in all cells. This drug is captured in cancer cells and does its main effect there. So that's the reason why this drug is If you look in preclinical data from the lab, this drug is much more potent than other alkylators and also more potent that dendalactylating entity that is released here. So, If you want to discuss more, we can do that in the end, but that's a sort of introduction to why this drug is a novelty when it comes to the mechanism. So we can move on to the next slide. And the study very standard randomized trial in the study design. Patients with relapsed refractory myeloma they had to have used at least 24 prior lines and the maximum CRYANISE. This is the typical setting for using pomalidomide today. They needed to be refractory to lenalidomide And I needed also to have tried the protosome inhibitor which are the 2 most standard drugs in the first lines of treatment. They were randomized 1 to 1 with equal number of patients in each group. The control arm pomalidomidex you see in red here was given in a standard fashion in the way we do use this drug in routine practice. It's a tablet you get days 1 to 21 in every cycle which lasts for 28 days dexamethasone weekly which is the same in the intervention arm. Been the intervention with Melifrufen. Merpruvin was given on day 1, that is just one day each cycle, the 1st day of each cycle of 4 weeks. And both drugs were given until the patients were not able to tolerate it on anymore or they progressed had a relapse from their myeloma or of course in some very few events withdrew from the study. The The primary endpoint of the study was like in most studies PFS, meaning progression free survival, which is the point that the patient either dies or have a progression of the disease and this progression free survival was assessed by an independent committee not participating in the study in other ways. Of course, there were secondary endpoints Like in most these kinds of studies, we looked at both safety and overall survival and also the overall response rate. So next slide please. The baseline characteristic of the patients were well lens meaning that the groups looked very similar. You can see on the top that the median age of patients were about 68 ranging from about 60 to 72. And previous lines of therapy was a median of 3. So that means that the largest fraction of the patients had 3 previous lines of treatment. And looking at the characteristic, in other terms, it was quite what you expect from a patient population between 24 previous lines. If you look at the box on the bottom, you see that 50% of the patients had received a previous transplant. And this is an important number to take note of. Otherwise patients were refractory to alkylator about 30% of them. With lenalidomide almost all or in practice all patients were refractory to lenalidomid which is not so strange since this was an inclusion criteria. 2 thirds were refractory to a protosome inhibitor and about 20% to anti CD38 monoclonal antibodies. Was a slight the higher degree of triple class refractory that means that you are that the patients are refractory to both emits and protosome inhibitors and anti CA38 antibodies with 16% in the merloflufen arm versus 12% in the pomalidomide arm. Next slide. Next slide, Dario. Thank you. Overall response rate is the number of patients who or the fraction of the patients who has response that we can measure with at least 50% reduction of of the tumor loads measured by monoclonal components and free light chains. So this overall response rate was 33% percent in the metrolufin arm versus 27% in the pomalidomide arm, so it's slightly higher. If you look at clinical benefit rate which is all patients that had at least a 25 percent reduction in their tumor loads. This was also higher than the menfluid arm with 50 versus 41 percent. And if you look at the different types of response, the complete response is that you don't see any anymore of the monoclonal component and you have low number of cancer cells in the bone marrow 3% versus as the 3% versus 1% and also for vGPR, which is 90% reduction, partial response, which is 50% reduction and minimal response, which is 25% In all these categories there were a high number for melflufen decks versus pomalidomidex. So next slide please. This is the primary endpoint. So this is what in the sort of Most studies define if a study is a success or not. The primary The progression free survival of patients on melflufen dex were 6.8 months versus in pomlithmidex this was 4.9 months. This is a hazard ratio of 0.79 meaning that there's a 21% lower risk of getting progression onmelflufen Dex versus pomlitimidex. You can see the p value is 0.03 which means that this is a statistically significant result and a result that means that it takes longer time to either progress or die with merflufen than pomalidomidex. So, and this is also this was assessed by the independent response committee and not by the study team or the study investigators themselves. So, next slide please. Looking at subgroups, you can see that if you look at the dotted line, vertical line at the place of the one number. You see that if you are on the left of this that means that this subgroup was Wimal Flu and Dex treatment. This is for PFS. And usually subgroups Are in line with the ITT population that is the total population result where we saw that it was a PFS benefit of merfleofen. But in a head to head study this can be a little bit different than in an add on study. So we can find some interesting results here. And I would like you to look at first the age category in the top where you see that the oldest patients benefited the most from melflufenex And the youngest didn't benefit at all. You see the dot is in the right on the dotted line. And this is probably, we think connected to what you see in the lower box where you see that patients with a previous transplant And that is patients that are younger, they did not benefit from melflufen Dex and the result was the same in both groups. But if you look at patients who did not receive a previous transplant they've been benefited significantly from treatment with melfrufindex. So I think probably this age groups and the previous transplant are the same thing since elderly patients do not get in most cases a transplant. And for the other results, it's not so much to comment. If you look at the only dot that's really on the right side you see that the confidence interval is really huge and that's because there were very few patients in this group so I wouldn't put Too much emphasis on that. So, next slide please. This is maybe one of the more interesting slides here because here you see that The 2, this graphs are PFS, so it's the same as the previous one but now we have divided both the merfleufin dex group and the pomalidomide dex group into those who had received a prior transplant and those who didn't those who hadn't received a prior transplant. And as you recall, transplants were given to about half the population so these four groups are more or less similar in sites. And here you can see that the 2 red graphs formulate the METex with and without the biotransplant perform more or less equally. And they also perform more or less equally with Menflufen Dex with a prior transplant. But the group that really separates from the others are melfrufindex that had not received a prior transplant. And just to mention that, I didn't mention that before, a transplant is all is also an alkylating agent. And then transplant sometimes puts some long term stress on the bone marrow And that might be an explanation for this. But anyway, what you see here is that the group that has No prior transplant and received fluvidex is definitely the group in this study that benefited the most. So that means that it's this group that drives the PFS benefit that was seen in the total population group of melfrefundex. You can also see that In the median PFS, the difference is larger here than it was in the total population with 9.3 versus 4.6. So the hassle ratio is larger, it's or smaller, it's 0.59, meaning that there's a 41% reduction in risk of progression or death and you also see that the p value is highly statistically significant. Yeah, next slide please. And when I look to this into more detail, you can see that this is On the top you see the patients with a prior transplant, on the bottom you see those with a not the prior transplant. Those 2 were in the previous forest spot with all the other subgroups. But if you would divide the prior transplant into patients who had received prior transplant very recently within two and a half years. Those who have received a prior transplant before 5 years ago, more than 5 years ago and in between those between 2 and a half and 5 years, you see that this is, you see the trend all the way that The longer time that has passed since you have the transplant, the more you benefit from melfrufindex. This is only significant for the ones without the prior transplant, but also for the ones with more than 5 and 2 and a half to 5, the PFS benefit trends toward melflufen. So next slide. This is over survival and this is what has led to the clinical partial, the partial clinical holds of FDA which class discussed in the beginning here. What you see is that you can see on the right that this is not a statistically significant finding, But you also see that the hazard ratio is 1.1 and that pomalidomide is the in the red is the group that numerically has a higher survival. So, this is the reason that that clinical hold was started and FDA are looking more into this data together with oncopeptides. I will show you some of the data they are looking into. So next slide. Here we have the subgroup analysis of overall survival and if you look at age first you see the same as for PFS that the patients who are the oldest They benefit significantly from getting melfrufen and those who are the youngest benefit from comolitimid with those in between not benefiting more from the from one or the other. For the rest of the subgroups here there's not so much Interesting findings actually they are all groups very close to 1. So if you go to the next slide, Here you can look at especially the previous transplants which we have discussed for PFS. So So if you look at that, it's the 3rd from the top. You can see that those who have experienced a previous transplant do benefit from pomalidomide While the patients who had not received a previous transplant benefit from Melflufen Dex, This funding is not statistically significant but it's at least not the other way around. You can also see for the alkylated refractory in the next line trends towards having a benefit of merflufenex which is important since this also has an alkylating mechanism. So that means that being refractory to alkylators Is in itself not a reason to not use Menfluid index, almost the opposite. And on the bottom you can see over survival when it comes to renal failure but those data are a bit Confusing because some of the groups are very small but it's it trends towards less renal failure or normal kidney function benefiting formalidomide and the other renal failure benefiting maleflufenex to a higher degree but the last group is so small that it's difficult to discuss that point in particular. Next slide, please. These are the over survival Kaplan Meier curves. We have already looked at the subgroups and you so the hazard ratios and p values was already there but here you can see it more visually. So if you see on the right, If the patient has received a prior transplant, homiletimidex is definitely better for survival. And if you look on the left, If you have, if the patient has not received a prior transplant, miflufen is trending towards a better survival and this trend is stronger than the trend for pomalidomidex in the in the total population which led to the partial clinical hold. You can also see if you look at patients who have not received prior transplant. And you see below there, you can see that the median OS is 21.6 versus 16.5 months. So with a 22% reduction in risk of death, but the opposite is true for patients with a prior transplant. So, next slide please. These are the same groups that we looked at for PFS and now it's for OS. You see on the bottom you see patients with no prior transplant and on the top of those with a prior transplant And you see that, well as what we have mentioned already that if you have not had a prior transplant OS is favored by using melflufen dex and, Poindex for those who have used a prior transplant. You also see here that the longer time that has passed since the transplant, the more you benefit from melfrufen and those who have more than 5 years of time since their transplant also yet on the melfrufen side here of the line. So next slide please. Yes, so this is efficacy, I mentioned this briefly, this is efficacy in non transplant alkylated refractory patients because There's a discussion whether mefllefin is just another alkylator or if it has something extra that other alkylators doesn't have. And this is important because there are other alkylators on the market that are available and of course cheaper since they're generic drugs and also used to somewhat degree in myeloma treatment. So, what you see actually here is that If you look at only the non transplanted because we already seen that those are the group, that is a group that that Melforfin is benefiting the most. I mean, if you look at that group, on the right here, those who are also allocator through. That means that they have used an alkylator before that is Melflan or penamustine or cyclophosphamide and have progressed on treatment with that alkylator. You can see that on the right top here that if they received maflufen dex in this study versus pomalidomidex, The difference in PFS was 8.3 versus 3.8. That's actually a large difference than in the total population and the median over survival is increased from 13.1 with pulmonary med Dex to 24.3 with melfrufen Dex. So So a very strong signal that it's the transplant that is a problem for merfrufam patients not to be refractory to other alkylators. And it also suggests that this drug actually is a different thing than the other alkylators that are on the market since patients relapsing on these other alkylators are getting this large benefit from, Meliflufen. So, next slide. Also looking here at when the patients died and if you look at the top orange box, The number of deaths in the total safety population that is between all patients that has tried the treatment that received the treatment in the study. It's 46 versus 43%, so a little bit higher from elforaphane but not much. And you see that they, death before 30 days after last dose that is what we sort of define of, as on treatment. It's It's a little bit higher for Comdex at 13% versus 10% and after more than 30 days after last dose is higher for melflufen 36% versus 30%. So it means that the excess deaths of mefluffin at least some of that comes after the treatment has ended. One for pomalidomide, maybe a little bit more while on treatment. I can also show you something that It's a bit complicating is that if you look on the top here you see that 246 patients were randomized to my proof index but only 228 received the treatment and that difference is much smaller from the Poindexter arm and we don't have the total explanation for that but those are patients who didn't receive the treatment but they are still counted overall survival group. So next slide please. When it comes to adverse events in this treatment, it was definitely mostly hematological. You can see there's there's more thrombocytopenia in the mallefrufin group, but not much bleeding. We only saw 1 percent of a severe bleeding in these patients in the melfrufen group. Neutropenia was higher in the melfrufen arm but infections were higher in the pomalidomide arm. So it doesn't seem that this neutropenia leads to infection or this higher degree of neutropenia doesn't lead to a higher degree of infections. So pomalidomide had much infection more infections in all the way we counted infections in total grade 3 and 4 infections infected pneumonia and grade 3 and 4 pneumonia and also with concomitant attempt neutropenia. Anemia was more common in my trofin arm but anemia is not something we have a particular problem with managing in the clinical on the clinical side And there was not it was not many and equal numbers of new malignancies during the study. Next slide please. If you look at adverse events that were not hematological and not infections, they were not very common at least not in grade 3 and 4. So I'm not going through this but it's very small numbers. So what you can see on the bottom is that those delays and reductions were more frequent in the melflufen arm And this is I think part of managing this drug is that you need to sometimes dose delay and sometimes reduce the dose to be able to have the patient's own treatment. You need that with all drugs, but as you see here a little bit more than flu for them and pomalidomidex. So, next slide please. Concluding, this was a head to head study of melflufen dex versus pomalidomidex which is not very common in myeloma. Merfrufen dex was still superior to pomalidomide dex for the primary endpoint of PFS. OS trended in favor of melflufen plus dex in patients without the prior transplant and favored pomriddimidex in patients with the prior transplant. So, a quite sort of dichotomy in these two groups that both was half of the population in the study. The safety was as were as has been reported before on this drug with mostly hematological adverse events that are manageable. It's not a drug that has many other symptoms for the patients. So the result in my opinion shows that In this group with 2 to 4 prior lines of treatment even who are refractory to lenalidomid. Niflutin dex is a better drug for patients who have not received a transplant while comalidomidex is a better drug for those who have have received the transplant especially if it's recently. So I think that was all or is there maybe an acknowledgment slide on the end here? No. So, thank you. I'm open to take questions My comments? Thank you very much, Doctor. Jeswald, for this very comprehensive overview of the OCEAN data. I see that a lot of questions have already come in and we'll try to answer them all. Some of these will be answered during the Q and A on the end when it is clear about the regulatory strategy, etcetera. So, I would encourage Everyone in line to submit questions that are relevant from a clinical perspective so that we can now that we have Doctor. Cheslop with us so that he can share his expertise with you on some questions. When I start with one of the questions, it is from Patrick Ling. Regarding overall survival, Do you have any data on what subsequent treatments the patients got? And were there any differences between patients receiving Pepecto and pomalidomide and could that then maybe explain some of the difference in OS outcome? Doctor. Jesnels, what's your view there? There were an unbalance in subsequent treatment. There were more patients receiving CA38 antibodies in the pomalidomide group and there were more patients receiving pomalidomide in the melfrufen group. So there's definitely an imbalance there and we also have data showing that the patients received ratumumab as the next treatment where doing the best of the patients that were treated afterwards. So there is data suggesting that there's a bias there that can drive the overall survival the wrong way And we also know that it's only about 20% of the patients were refractory and probably not more exposed to CA38 antibodies before. So it's a bias there. Personally, I think it's always very complicated to start discussing that because if you had the patient who received melfrufen in routine practice and you had the patient who received melfrufen in a study. When they are out of the study or getting a new treatment in routine practice, the same sort of decisions are being made. So if you were going to use that as an argument, you would have to say that, you should, after melfrufen, get daratumumab instead of pomalidomab. And that's sort of a difficult case to advocate when you want the drug approved and reimbursed. So personally, I think it explains quite a lot, but it's very difficult to move on with that argument, I would say. So I think it's much more Important to focus on the subgroup, the large subgroup that really benefited from melfrufen disregarding subsequent therapies And that is the question of transplants. Thank you, Doctor. Schestfeld. We have a question from Peter Welford from Jefferies. As to what would be a possible explanation, so what would be a mechanistic or biological rationale for why a prior stem cell transplant drives this delta? A transplant It's not good for the bone marrow. So we know that it can take time for the bone marrow to recover fully and to common normally functioning bone marrow again. I think that is the time issue. I think that if a number of years have passed, I think the the boner is more normalized at least on average also depending on further treatment of course. But if you have performed a recent transplant, I think The tolerance for an alkylating drug like melflufen is lower. I think that's the main mechanism. I think It's difficult for a bone marrow that has received a transplant in the recent couple of years to tolerate Melfrufen. I think that's why we see more deaths of Melfrufen in the Melfrufen group after they have stopped therapy with melflufen because I think that when you have the combination of melflufen over event. And then, melflufen, your bone marrow will have struggles to tolerate treatment afterwards. So I think the treatment afterwards will be probably less tolerated, more dose reduced, And more stopped. I have to say that this is a speculation. It can also be clonal selection from the transplant, Which is more important the closer it is to this clonal selection that's also a possibility because I do think that the transplant, which is a very high dose of of nagulating agents and Melfrufen, which is locally in the cells a very high concentration of an alkylating agent. They are probably selecting some of the same cells. But I do believe more in the first that it's difficult to tolerate this to tolerate subsequent treatment if you first ever transplant and then within not so much time, merfrufen. And I also think it also sort of goes back to the point with the subsequent treatment because we know that pomalidomidex which is a more pulmonary suppressive treatment than there are tumor and pomalidomidex was more in the melflufen arm than in the pomlidinib arm which got more daratumumab afterwards. So it's it can also be a factor there but Main answer for me is the bone marrow tolerance is too low for merflufen with a certain time of recent transplants. Thank you. Thank you very much. We have several questions on one topic, which I think is important To highlight, also from Adam Carlson is what proportion of multiple myeloma patients in the real world I should undergo a stem cell transplant and what would be potential trends there? The proportion today is, I would say, about 40% or something like that because this, you know, the median age of myeloma diagnosis is around 70 And not many centers perform transplant over the age of 70. That means that 50% just disappears there, even though there are some exceptions who do give transplant to elevate, but that's not enough to sort of see in the statistics. And also under the age of 70. There are a fraction of the patients maybe 10, 15% that are not eligible for transplants. There are 2 trends. 1, that is it's not, It's not even a trend anymore. It's much more established now than some years ago is that 10 years ago, it was quite common to give a transplant at relapse. So we gave a transplant in first line and then you gave a transplant in second line because we didn't have that many drugs available. So that has been becoming much more much less common. So not many countries do that in many patients now. So that means that for the average patient, the time to the last transplant will be longer in a certain treatment. The other trend is that we have done studies to eliminate transplant for a long time. But so far, the studies have not seed it. I think the closest was the largest, the most recent, the IFM 2,009, which showed that there's no even though there was a PFS difference in when they treated with VRD induction and transplant and maintenance versus only VRD and then maintenance. There was a PFS difference but not an over survival difference. I have to say that in this studies, in that study many patients got transplant at relapse. So it's mostly being used as argument for it's possible to delay relapse. But what has happened The last couple of years is that bispecifics and CAR Ts have shown response rates and PFS results in late line of treatment that is totally unprecedented. It's extremely effective drugs. So now very many studies are being set up in first line that includes these, these drugs, 1 or more of these drugs and eliminate transplant. Some are randomizing against transplant and some are just doing studies with these drugs without transplant. I'm planning to just so show that the results are better than the transplant. There's also been Several papers the last couple of years that has showed that transplant is inducing a lot of mutations that leads 2nd diagnosis later. And now we see that life here, so the total survival of Malone patients has moved up from about 3, 4 years to maybe 10, 15 now in the best centers. So that means that to get the second malignancy from the transplant treatment is much worse now than before when your life expectancy was lower. So the general trend is to move away from transplant definitely but the studies first have to succeed in doing that and so far They haven't, but I think it's a quite general impression that when we see data from bispecifics and CAR Ts in first line They will prevail over transplant treatment and transplant might be At that point, actually not so relevant anymore. In the elderly, the best treatments now in First line are without alliculators, that's dara revlimid. And the best treatments in relapse are without alliculators. So today in the patients who do not receive transplants, they are, if they are treated as guidelines suggest They are mainly treatment totally without alkylators for several lines of treatment. Hope that answered the question. Thanks, Doctor. Jeswald. I have some questions from Patrick Linge from DNB, but I think one important one to touch on now and we'll come to the other questions of you, Patrick, later. It's about the cross resistance between lenalidomide and pomalidomide. We've talked about that before. And how did that play out in the OSHA trial? The resistance profile materializes as you had expected. I think sort of, we know that pomalidomide is a better drug than lenalidomide. We know that it's more efficacious and we also know it's better tolerated. We also know that the response rate is not far away from where it's in this study in those populations from earlier studies. And I think a response rate of 20 7% in the venolitimide refractory patient is more or less what we would have expected I would say and also for the PFS of about 4 months. So I wasn't very surprised by that. It is a better drug. In many patients, it doesn't work in lenalidomide refractory in patients. But it does work in a significant fraction of the patients and that's why we That's why pomlutamide is a standard in this population that alenolutamide refractory. And I've seen Of course many patients in this situation and I see patients who just doesn't respond at all and I see patients who have a tremendous response pomalidomide after being refracted to lenalidomide. So, the cross resistance is there, if you because if you had if you Give pomalidomide to patients who are not refractory to Revlimid, their response and PFS are better. But I don't think the Palmdex data here were very surprising. Thank you. And I would like to take another 2 questions here because you're also mindful of your time, Doctor. Jeswald. And I have a question here that I think we could either Fairly quickly, but could you comment on whether we saw any differences in secondary malignancies between the Melflifen and the pulmonidomide arm? There's no differences and very few events in both the groups. Yes, very good. And so So the question is that could it be a possibility that daratumumab is particularly given in a higher extent to younger patients resulting in the advantage for the overall survival for bromalidomide. Could that be the reason from your perspective? It's possible. I think In countries, I think you would have to look at the data for this in which countries this was happening and then what age groups the patients got daratumumab because it's if you have countries where daratumumab for instance is an expensive drug and pomalidomide is equally expensive. I would think that most doctors would give daratumumab if they had the availability. Could also be that the availability of daratumumab pomeremib wasn't the same in all centers. It could be that If you make a choice of melflufen, you have a choice in addition to the others. You have PROM, you have DARA, and you have doctor's decision will always be based on many things. So it was always clear that more patients in miflufen would get pomalidomide in any case. So I think it's very difficult to answer that. You would have to look at if the patients who received DARA was younger. It might be but I don't know. But I think a study needs to show its results as they are. And if you speculate too much on what comes afterwards, it's It becomes very difficult to argue for a drug, then you would have to argue that the miflutide would only give a benefit if you gave daratumumab afterwards, which is a sort of strange path to take I would say. So I think it's good to look at all this data. I don't have the data you're asking for there. The age of the daratumumab patient is possible. But daratumumab monotherapy, if I were to choose between daratumumab monotherapy and pomoratumumab dex It's not that clear that tarratumumab is necessarily better because tarratumumab's efficacy is mostly in an earlier alliance with combination treatment and as a monotherapy its efficacy is not that much better than PoMS. So Yeah, no, I'm just babbling here because I thought I don't have the real question to the answer, but I'm not sure that's That's the explanation. Let's put it like that. Right. Yeah, and I've been able to quickly look at some of the data. And to answer the question directly here, it doesn't seem to me to be too much differences between age and the frequency of daratumumab being given. So it's more the age as such that drives or is more likely to be connected with the transplant then the use of daratumumab according to age groups. I'd like to highlight one final question for you, Doctor. Schaszfeld, and I know we're over time, but from Christopher Ude from SAB. Doctor. Jeswald, in your view is the proposed mechanism of PePexto beyond dispute given the human PK profile and given the secondary malignancies being broadly similar to pomalidomide. It's beyond dispute if you look at secondary malignancies and Can you repeat the question, Wamskar? Yeah, I think the and I'm trying to clarify, if beyond given what we see that there were no differences between pomalidomide and noflufen in terms of the rate of secondary malignancies And given the preclinical data that is out there, is there any reason to believe that it is really a different drug. So, it is beyond every doubt that this is another drug when compared to other alkylators. I think when you're talking about secondary malignancies, I think You have a follow-up of 15 months and you have 2 drugs that both give secondary malignancies. We know that both the image and the regulators do that. So, to have a difference between those 2 in a period of 15 and a half months is impossible. What you see in secondary maintenance is usually they come after several years. So, I don't think that a low and equal rate of secondary malignancies, good impact on the belief in the mechanism. I think the most important part that makes me believe in the mechanism It's actually from this study and it's that The benefit is so large in the alkylated refractory patients, those who are refractory to Melflon, those who are refractory cyclophosphamide and bendamustine. So, I think that's the most important data to answer this question since this question popped up Several years ago when merfrufen first started doing studies, it's been asked how is this better than other, alkylters or different from the other alkylators. And I think The most important data are actually in this study that the benefit is so large in the alkylated refractory population both for PFS and for OS versus pomeridamid. So I believe in that more now after this study than I did before this study when we didn't have such data to look at. And we know the mechanism works like this from preclinical studies. What we don't know is How that translates into clinical findings? And I think the efficacy you see here in alkylated refractory patients Are sort of confirming that I would say. Are you talking, Claus? I can't hear you. Sorry, I wasn't on mute. Thank you, Doctor. Jeswald. I think we still have a lot of questions pending that we will be happy to take. We'll also address some of the questions in the follow-up part of this webcast. For now, I would like just to thank you for your time to not only present the data yesterday during the weekend, but also here with us today during this webcast. That's much appreciated. I just wondered if you had any final thoughts you would like to share? I think we touched upon The most important parts, I would say. Okay. Then, thank you very much, Doctor. Schaszwold. Hope to speak to you soon. And then we will continue with the release. I can say that I've been asked Several times the last couple of days what will the FDA say? And I cannot answer what the FDA would say. It's always difficult to know that sort of things. But what I What I think they should say, I think they should say that this drug is is beneficial for non transplanted patients and let's move on with them. Like they did with venetoclax and belini, they said this drug is very beneficial for the 11.14 patients. Let's move on with that, both of the studies and with approval. I think that will be what I think they should say based on this data. Thank you very much. And we'll speak again soon. And then I think we can move on with the rest of the webcast. Thank you very much and have a nice evening, Gokce as well. Yes. Thank you. Bye bye. Okay. So, thank you all for listening in. We have some other slides that we would like to share and I know there are still a significant number of questions pending and I will try to touch upon them as we go along and otherwise we'll take them during the Q and A in the end. So, if we go to the next slide, please. So, we have mentioned the ODAC meeting earlier and we have also sent out a press release on that. And the purpose of the ODAQ plan for the 28th October is an update basically on Ocean where we showed a hazard ratio of 1.1 in favor of the control arm polynidomide And there will be a general discussion on what would be the appropriate next steps for the product and you've just heard Doctor. Jeswald's view and whether the indication should remain on the market while additional trials are conducted. So that's really the purpose of the ODAC on the 28th October. Next slide, please. So, if we then zoom in a little bit deeper about what actually is an ODAC meeting. Well, it is a committee of 13 voting members, including the chair, where data concerning the efficacy and safety of drugs, whether they are on or not yet on the markets, are discussed and where the panel will then make appropriate recommendations to the FDA. The committee generally consists out of experts in the field general oncology, pediatric oncology, hematologic oncology and also some very technical experts. The vote is very informative and often the FDA follows the direction of the ODAC committee but Please note that the vote is non binding. This committee is really to give guidance to the FDA. Next slide, please. So, what would be potential outcomes of the FDA review, including the ODEK? And I've seen a couple of questions coming by where I will try to touch upon. The answer right now is of course that we don't know the outcome. But what we do know is that the FDA has signaled a level of concern around the overall survival data. We believe based on communication with the FDA, which has been quite extensive over the last couple of months as you may appreciate that we still believe there is a possibility to end up with a label that includes 3rd and 4th line use of the drug, but then with a restriction, for example, for non transplanted patients or better set for stem cell transplanted patients so that it would include the non transplant patients in 3rd and forward line. A second scenario is where they say, well, this is a very interesting hypothesis and it warrants further study in your development program. And in that case, it could be that we would have to verify the benefit in another study. However, it could also be that that would lead to a potential another accelerated approval based on the ocean data which then needs to be confirmed. So that is also a possibility. And then we have a worst come outcome and we mentioned that specifically because it is mentioned in the ODAC briefing message that should Perpaxto stay in the U. S. Market, we see this as a very unlikely scenario, but we mentioned it and that is withdrawal of vaccine from the U. S. Market. Of course, during all these communications with the FDA, it's not unlikely that during the coming months, the current Horizon label will have a safety update based on the data from Ocean, but to what extent and how that is currently impossible to comment on. I think it's in general very important to note that the Horizon population was a very late population, so even though patients were included that had had stem cell transplant. These patients were often beyond the 5 year window and that makes that you cannot compare or translate the OCEAN outcomes to the Horizon label and for that reason I also not dare to speculate about an impact there since this is truly a different patient population and we strongly believe there is a good likelihood that we will be able to continue commercialize in the 4th line plus heading there. Next slide, please. So, a timeline And we have compressed it due to the numerous events over the last couple of months. So, a lot has happened since the top line results. The initial top line results were disclosed on the May 25th. We have seen the issuance of a partial clinical hold, the safety alert. And now we are at the stage where we have just presented the data to a broad scientific audience. And the interpretation of the data is quite homogeneous where we see responses not only from Doctor. Jeswald but also from other key opinion leaders where they think it is plausible what we see because there is a biological rationale And there is an important place for nelflefin in a non transplant setting and That is especially because of the high unmet need and I will talk about that in a minute. Then we have the clinical response letter that is pending. We aim to submit that in the coming weeks and then we have an ODAC meeting on the 28th October. One of the questions touched upon the fact whether there would be a response to the clinical response letter before the ODAC meeting given that the FDA needs to issue a response within 30 days. We cannot we can only speculate about that since response data can also hold information that they want to await the ODAC meeting and that would could be their response. So, that would be pure speculation to say if we would get Kind of more information before the ODAK. What I can say is that we have submitted 5 abstracts with further deep dives on data on Ocean and we very much look forward to present these at ASH in December. And in December we also anticipate the publication of OCEAN results but this is of course pending review and acceptance by the medical journal. Next slide, please. So, if we look to the profiles of these non planted and transplanted patients and I think this is a key slide to remember if we look at the real world treatment landscape. We then see that non transplanted patients are generally older and that's also what we saw in the forest plots where we see a clear signal of nalfluthen being more efficacious in older patients, even significantly more efficacious and that is because they are non transplanted patients, but that means that these non transplanted Patients are generally older and if you look at the fact that the average relapsedrefractory multiple myeloma patient is a 70 year old patient and then starts its treatment in the RRMM setting, you can almost Deduct that that is the majority of the patient population. The performance status because they are elderly and more frail is somewhat lower And we see that they have had the same previous exposure as in Ocean other than that they have received regular dose alkylators and not the high dose melphalan used for the transplant, which is of course part of the story for the transplanted patients who are in general are much younger, that's also the reason why you see that the patients who benefited From pomalidomide, we're in the majority below 65 years of age, which is the population that is generally being transplanted And these patients generally are in a somewhat better condition. If we go to the next slide, And this is a very recent study published this year. We look at the prognosis for patients in transplanted versus non transplanted patients. And importantly, to say this is after their first line treatment. So on the left hand. You see the survival probability on the x axis or in the y axis. Well, on the x axis, you see the second line overall survival. And why did we take it from the second line treatment? Because the transplant in itself is considered a treatment that is different from another. So you start to actually measure from the fact when the transplant has worked out in the first line versus people who have had their initial treatment but were not transplanted. And you see if you look at the median PFS that is 46 versus 28 months and that speaks To the green curve, the non transplanted patients where there is so much to win and so much to gain and what we see there with the 9.3 versus 4.8 months PFS, which also translated in an overall survival benefit with the same magnitude 5 months delta That is very important to take into account when looking at these OCEAN data and what it means for the real world practice. These are patients that are older and have a high unmet medical need. Next slide, please. So, again, to reemphasize this, we see here the differences as pointed out by Doctor. Jeswald earlier Where you really see no difference between pomalidomide and MELFLUFA in the transplanted patients, Whereas in the non transplant patients you see clearly the benefit of melfluthen with a 9.3 versus 4.4 month or 4.6 month for pomalidomide. So this is just to reemphasize that and as Doctor. Jeswalz had mentioned before, melvalonflufenamide in alkylated refractory patient is 8.3 months versus 3.8 months for omididomide. So very clearly speaking to the differentiated profile of maflufenexter. Next slide, please. So, this is something that Marty may also touch on in his closing remarks and where Doctor. Chessel talked about extensively, that is what is currently the treatment landscape when we look at the non transplant versus transplant setting. Well, the basic message is that if we look at the non transplant setting in the U. S. It's about fifty-fifty, in the EU it's about sixty-forty that in the next 5 to 10 years we anticipate that medical need population in the non transplanted setting only to grow and as such very relevant for milfluthen. Next slide, please. So to shift gears a little bit and I will come back to some of the questions on Ocean. Don't worry, but we'll first finish this part of the presentation. We also presented data from PORT at IMW and that was very important because So far, naflufen had been administered via central catheter. But for patient convenience, It would be worth to see whether it would also be possible to give it via a peripheral catheter, so without having a permanent access. We go to the next slide. So, PORT is a very elegant Phase 2 study I would say. It has a solid design and if we look to the upper right hand study design you see that these are all patients relapsedrefractable multiple myeloma, have at least 2 prior lines of therapy and were then randomized to get either beflonflufenamide via peripheral catheter versus a central line. But what happened then is that the same patient in the next cycle would get it via the other mechanism. So the patients who have got melflufen first via peripheral catheter, then got it via central catheter and vice versa. And this means you have the inpatient control, I would say, which gives you the most reliable data, especially when it comes to pharmaco kinetics because we also wanted to know given the high lipophilicity of melflutin where there's any differences between administration centrally or peripherally. And this is the study design, 20 patients and as said focused on the PK, but also on local adverse events Since moflufen can be considered a local irritating cytotoxic, it's important to also exclude that you will have negative consequences from peripheral administration. Next slide, please. So, a very complicated story told very short in this slide. And that's only because you need to look at the right graph where you have the PK AUC curve basically between PVC, so peripheral and CVC central. And as you can see, this is in 19 patients, but even with this relatively small sample size, you can already see that the lines are almost overlapping. So that means that we are confident to state that there is no difference between the profile of the drug where you administer it peripherally century, which is of course very important. Next slide please. Other conclusions beyond the same pharmacokinetics is that there were no and that means 0 local reactions after the referral administration of nofluthen. Not one single grade 1 adverse event And it makes us very comfortable to also, from our perspective, consider pre referral administration safe. This is of course and this speaks to one of the questions that I saw coming through off label because in the label it's considered to be in the instructions of use to be a central line But it needs to be an updated label, so will we submit an sNDA on the on the poor date? Ultimately, this will be part of a sNDA, Yes, to get the label updated. Whether physicians want to use it already right now peripherally, that's really up to the prescribing physician, but please note that that would be outside the current label. But These data are public and people are of course free to do with the data what they judge is in the best interest for the individual patient. So that's basically the story of PORT, very encouraging, will be used for an sNDA so that it also allows pemoral administration. Next slide, please. Marty, I think it's up to you now for some concluding remarks and then I think we can pick up the Q and A again afterwards. So happy to hand over to you. Yeah, thank you very much, Klaus. And again, thanks to Doctor. Schestfeld. Next slide, please. So, the slide in the top left hand corner. You've seen that a couple different times. And, you know, Kloss very nicely suggested on port, there was one picture that told the story. And I think this is the picture on the OCEAN trial, looking at the primary endpoint of progression free survival, seeing that absolutely all the PFS differential we see in the non transplanted patients in the benefit of melflufen Dex. And want to reiterate the point that was so nicely brought out by Doctor. JustFOLD regarding the alkylator refractory population and that differential, in terms of a 5 month delta between the Melflufin decks and the Palmdex arm in alkylated refractory patients holds up, and really appreciated, Doctor. Bulge view on how the novel peptide drug conjugate, pipaxto, delivering an alkylating payload is really proven out here in a head to head comparative trial, very nicely translating what we've seen from preclinical evidence on the differentiated activity of melflufen over the past several years, and we're continuing to be committed to that work. I also think it's interesting to point out, and perhaps we will play this out in a slide in the future, thinking about that time to transplant because when we take those patients from time to transplant and play that out, We see a very consistent clinical result playing out over the entire population of the OSHAEN trial, where secondary endpoints like, or primary endpoint of PFS and the secondary endpoints of overall response rate, depth of response, and overall survival absolutely align and tell a very, very common story. So, the conclusions that Doctor. Sheffeld mentioned from the stage yesterday and today, Phase 3 head to head study. Superior outcome on the primary endpoint of PFS across the intended population. The overall survival trended in favor of pomalidomide in patients with a prior transplant, plant but favored, melflufin in the non transplanted patient population. Safety on par for what we've seen relative to melflufin in prior clinical studies. And again, we look to reach conclusion with regulatory authorities, not only in the U. S. But around the world on the role that melflutphen or pacaxo can play in benefiting patients. So, next slide, please. So, a summary from the webcast here today. The data presented at IMW we would consider to be very encouraging. The OCEAN Phase 3 head to head study, the PORT Phase 2 study. I know there's a question in the chat regarding the applicability and when physicians can utilize this method of administration. So, we'll touch on that. Our near term focus is to reach agreement with the FDA. So, the ODAC meeting, as we've talked about, on October 28th will be important. There are a variety of outcomes. And obviously, we would align to Doctor. Schiefel's view regarding how he sees the ocean data and his thoughts regarding regulatory action of that. But we understand, appreciate the process and we'll work hard to reach that common agreement. In the meantime, commercialization of continues in the U. S. We are very pleased to hear patient stories coming in all the time regarding the drug's ability to help patients because that's what this is really all about. Also, we haven't mentioned the EMA, but that process is ongoing and thus far proceeding according to plan. And we look forward to ASH 2021. As Klas mentioned, we have 5 data presentations or 5 abstract submissions on the ocean data and I believe another 5 that deal with other aspects of our pipeline or preclinical work. And finally, in conclusion, on the right hand side represents part of the Oncopeptides contingent that was together in Vienna. Given the strange times from a global perspective. It was fantastic for myself to be able to meet such a talented group of individuals who are committed to advancing our product, advancing our pipeline and advancing patient care and really happy and pleased with the results of what we accomplished. So, I'll stop there and we'll move into the questions. And Klas, I know you've had the opportunity to stay very close in touch with the ones that are pending. So maybe I'll let you kind of sort out, the ones that you think are important and I'll also look through them as well. Very good. And then I will just start On the top, some very specific questions and I may answer them pretty soon. Bertrand Delzuk, have you already started to collect data over more recent data? Could submitted to the ODAC members or will the ODAC only review the February cutoff data? Thank you. This will only be the February cutoff data. Also, if we could provide more numbers on the Horizon population, so just the percentage of patients with a prior stem cell transplant. Yes, that is about 70% of patients, but as said most of this was a long time ago and since we don't see a detriment or even a benefit, I would say, in patients who have been transplanted before. We Do not see this as concerning for the Horizon population. Then Frederick Larsen asked Whether it's prudent to send the final response letter so that it forces the FDA to answer before the ODAC and would it not be better to submit the final response in the beginning of October. It's a very, very, very interesting question and good question. The only piece is that we are actually bound to respond within 3 months. So we also need to finalize our clinical response before the end of September, so that's not an option. Then Michael Svensson asked a very good and relevant question. With a large benefit on BFS in non transplanted patients, wouldn't it even be unethical and very tough to recruit a new study where these patients, if unlucky, would be randomized to pomalidomide? Very good question, very relevant question, that could be considered difficult. I am in full agreement with that and that also speaks to the discussions we're having with the regulatory bodies. If we need to confirm this finding into another study, how would such a study look like Given that the difference is so striking with 9.3 versus 4.8 months that you might indeed consider another design and not expose these patients to pomalidomide since that would be really harming these patients. Richard McDowell on what the management opinion is about the different ways the FDA is confused with percentage of ease weight. I would love to give that. I really don't have percentages and we haven't got the percentages on the table during discussions even. I think it would be and I'm just and Marty, chime in if you feel differently here, I think we feel broadly that another study to confirm in each or whatever way this finding is likely. However, whether that would be after a new accelerated approval in non transplanted patients or whether it would be based on a total new study. I really don't dare to speculate, but some kind of confirmatory study is likely in our opinion. And I already touched on the ODAC as such that we see it as a very we feel very confident that this drug will stay on the market. I would say that were my 2 main takeaways, new study likely and what form we don't know. ODEC, We are very optimistic there. Yeah, I would agree. I mean, there was a delivery session at IMW as well that we listen to with great interest, both FDA and EMA participating and the idea of the heterogeneity of multiple myeloma came up and the need to focus in on specific patient populations and clinical trials It is important. It's becoming a very crowded field. You know, I, again, I think we'll stand behind the data and work, work hard with the regulatory body. I mean, we see a very, very clear view of the data here. You know, some of the questions that came in asked about the overall survival in the treatment to treat population. And there are ways in which you can credibly explain away differences, subsequent treatment, patients randomized but not treated, and begin to chip away at that 1.104. But when you zoom out and take a 30,000 foot view of this study, I think it's pretty clear that, you know, we see the benefit of our drug being delivered in patients who have not received a prior transplant. In those patients that have gotten within 2.5 years, we see a detriment. And we certainly would move accordingly, being data driven, benefit risk driven, and look for that to be the outcome here. So, the science and data will rule the day in our mind and can put a probability of success on the outcomes. Yeah. No, very good. Thank you, Marty. I have A question from a private investor on the overall response rate in the non transplant subgroup. I don't know the exact number by hand, but it is in the 40% and higher. So also there we see this from a secondary endpoint perspective, we see the same trend being more efficacious in the non transplanted group. Then a question from Hampus time, who asked whether it's probable that the maturity of the dataset will render statistical significance in the OSHavre ratio favoring of lufine plus dex in non transplanted patients. Yes, given what we are seeing today, this is very well possible. However, of course, further cuts of the data is also something we need to agree with the agency. I just do want to remember everyone that this study met its primary endpoint and as such is successful. So, if you then also look and you see that in the subgroup of transplant or non transplanted patients to full PFS benefit is preserved in the overall survival. That is a very substantial finding. Of course, it signals risk in the earlier transplanted patients, but we see a clear benefit in the non transplanted patients and that may even render statistical significance. However, I strongly believe that is not critical for our discussions with the agency as because we are speaking about a study that met its primary endpoint and has a very significant benefit in this group of patients. Also on the ASCT, Michael Svensson asked whether was not a predefined subgroup as I understand it. It actually is a predefined subgroup. So this group as I understand it. It actually is a predefined subgroup. So this is not an exploratory subgroup, so to say. This was a predefined subgroup. And as said, half of the patients got a transplant. So this is not as in the BILIDI trial, Doctor. I personally think that this is a completely other study where the Bellini trial showed a hazard ratio of 2.0, whereas it shows a hazard ratio of 1.1 here with not just a subgroup, but I would say half of the patient population deriving a clear benefit both in PFS and OS. Hey, Klas, I also liked how Doctor. Schesfeld, and I think it was in response to a question, was talking about kind of the future and the trends. I mean, in our OCEAN study, we see about a fifty-fifty mix between the transplant and the non transplant planted patients. And his view was that less patients would be transplanted in the future based on the CAR T, the BiTEs coming forward. So, you know, our view is having a powerful novel peptide drug conjugate that is able to deliver what we call it a soft transplant or not is a growing opportunity as we would see it. And of course, it's up to us in our clinical development program to shape that, but certainly the landscape is set for that to be a possibility. There are questions that kind of ask about transplant and age. And, yeah, it was quite remarkable to see the subset analysis by age and the trends for both PFS and OS. But this is likely and we see a very high benefit for, for Popaxto in older patients. But that really in our multivariate analysis is really driven by the question of plant or non transplant. So, in terms of the biologic basis here, it's more consistent, we think, and more sound to be thinking about this differentiation of the patient population and where the benefit is delivered to think about it in the transplant versus non transplant rather than the age setting. All that being said, certainly a doublet with this kind of concentrated efficacy in non transplanted patients who are older is, I think, a good place for us to be and a place in which we can deliver a substantial amount of benefit to patients and patient care. Absolutely. And Marty, if you're fine, I just have a couple of questions in front of me that I think I can easy relatively fast. And that is about GK ask whether comments on risk for need for new clinical trials versus adjustments and use of the already ongoing studies and we also have the question on Lighthouse and whether the design would be changed. That is all very likely. I mean, we have found Some remarkable differences here. And when we talk about the response letter, that is about how do we want to pursue our current clinical development program and what would that mean. And from that perspective, it is very likely to think that indeed some study designs will have to be amended to this finding of the benefit of maflufen in non transplanted patients, but more importantly to exclude patients that have been transplanted early because that would be particularly putting patients at risk, which is of course not what we would do. Another question on the 18 versus 3 patients who were randomized but not treated from both Patrick Linge, but also from others whether that shouldn't be excluded. If you look in the safety population and that is really the patients where the 18 and 3 are taken out of the consideration. The hazard ratio goes down substantially and moves towards 1 and that is of course one of the arguments that we would or have already put forward to the agency as well since of course it is a particular imbalance that speaks to that. And then I see Christopher Ude from SAB, a significant PFS benefit in non transplant patients, but not an OS benefit. The only significant OS benefit is in older patients. I would dare come back to the question that this is a significant study. PFS is the primary endpoint, OS is the secondary endpoint. So that is not needed to show an OS statistical significance. However, overall survival is also a safety endpoint. And when the FDA speaks about their concerns, and this is purely from a safety perspective, so not from a registrational perspective, They see the transplant population as a risk population and we concur with that view and that's also how we present our data. That doesn't mean that if you met your primary endpoint with a subsequent trend in overall survival that you need now suddenly statistical significance in a predefined subgroup. So, significance in a predefined subgroup. So that is something that we would say is not impacting the chances of success. Then I would say Maybe given the time, I'm not sure if anything gear jumps out. Obviously, we're going to have multiple opportunities over the next several months leading into ASH. I think there's some investor conferences and, of course, 1 on 1 meetings that we can have to discuss results further. You know, from the OS and PFS subgroup slides, you can see there's a wealth of data. Ocean will be a story that keeps on giving. I think what you saw yesterday and today is really the high level view of what we think is the essence of this positive OCEAN trial and where we will continue to work with regulatory bodies in helping to, you know, conclude on a label for repaxto moving forward. So, perhaps at this point, we conclude the call unless anything else has come in. Claes, that you see that might be Interesting to pick off? No. Just one piece that I can easily answer, why some of the data that was presented today, was not presented at IMW yesterday. The answer is very simple, time constraints and number of slight constraints. We would have loved to also include these slides at the meeting yesterday, but you are only allocated a certain amount of time. But we felt it was appropriate to share it today with the analyst and investor community to even give a broader picture beyond what was shared yesterday at IMW. So, that's the very simple answer to that question. I think Doctor. Shesvold had 10 minutes for his presentation yesterday. He had 30 in this particular webcast. So, there was substantial more opportunity. So, again, on behalf of types and the team. You know, thanks to everyone for joining the webcast. We look forward to our future interactions and appreciate, you know, your continued interest in the story and digging into it and helping us move forward as a company. So, much appreciated. Thanks. Have a great rest of your Sunday evening and take care now. Bye.