Study Result

May 25, 2021

Thank you very much and good morning to everyone and thank you for joining us on this great occasion to provide the top line results for our Phase 3 OCEAN trial. We're very excited to communicate our thoughts in the top line results and implications for this fantastic outcome of a head to head comparison. So on Slide 2, I will be joined today by Jacob Lindbergh, our Chief Scientific Officer by Klaus Bacher, our Chief Medical Officer and by Anders Martenlauf, our Chief Financial Officer. And as far as the next slide and on disclaimers, of course, we will be making speculative and forward looking statements regarding our drug and our company. So we ask you to please look at our filings for the full risks and balances. The so slide 4, we're just so pleased to report these very positive results. The OCEAN trial is a positive study. And certainly with the outcomes that we're seeing as a CEO, I'll sign up for this outcome every single day. I think the key for all of us as investors and stakeholders in the company though is how will it be perceived by clinicians and regulators. And on that point, we feel very positive. We believe that this is a major milestone for relapsed and refractory multiple myeloma patients. And we look forward to the future communication of the final results and working with regulators to improve the label and expand our the availability of COPAXONE worldwide. So in terms of our key takeaways on Slide 4, the OCEAN trial. No one dare contend with the fact that this was a very boldly designed study with a successful outcome. And this is the 1st head to head positive trial in multiple myeloma in 6 years. And we didn't just choose any agent in terms of the head to head comparison. We chose the drug that is the most widely used drug in relapsedrefractory multiple myeloma that being pomalidomide. And on our top line results with the primary endpoint of progression free survival on the point estimate of median PFS. COPAXONE was 40% higher than pomalidomide. And as a reminder, pomalidomide has sales worldwide of $3,000,000,000 and is growing at 20% on an annual basis. When we set out with the horizon trial and passed the FDA hurdle and got accelerated approval for our drug the best in 5th line plus population. We suggested that we were starting a journey and we continue with the results of the OCEAN trial to be on a path to make this agent a foundational treatment in relapsed refractory multiple myeloma. As you'll hear through this presentation, we are working as hard as we can and as quickly as we can to present this full data set at conferences throughout the remainder of 2021 with the first showing as soon as possible in terms of being able to submit this and getting at the stage that it deserves. And we are already well underway as it relates to regulatory bodies and in particular the FDA in discussing our plans for supplemental new drug application for repaxo for earlier lines of therapy and to get this outstanding comparative data into our label. So in closing this opening here, thanks to patients that participated in this trial. Thanks to the investigators for this outstanding result. Thanks to you, the investment community for making it possible. And also of course the Oncopeptides team that executed this trial flawlessly through a global pandemic with certainly an outstanding result. So on the next slide, I'm going to turn it over first to looking at the agenda to Jacob Lindbergh, the will take us through the top line data. I'll come back with the commercial opportunity and then we'll move to Q and A. So with that, I'll turn it over to Jacob Lindbergh. Thank you, Jacob. Thank you, Martin. Jacob Lindbergh here. So please go to Slide 6. Before we look and talk about the results in the next section, it's worth doing a few reflections around what type of trial this is. The vast majority of trials in oncology are so called add on trials and we'll come to that. The and as Martha just mentioned, the OCEAN trial was head to head. It's a head to head comparison, which is actually in myeloma quite rare. And on top of that, when you do a head to head, it is rare to also do it with a full blown relative a relevant comparator, in this case with pomalidomide that is as close to standard of care in relapsedrefractory multiple myeloma as you can come. However, there's a challenge in doing these both trials and that is because the dominance of the add on trials is such that most developers and clinicians instinctively interpret results and to some extent also the market regardless of the design us through the lens of add on trial outcomes. And as an example, when you have a hazard ratio 1 in an add on trial, it means your drug is doing 0. Hazard ratio 1 in a head to head trial means that you are equipotent with the drug you're comparing with. The statistics are the same, but the interpretation is vastly different of the same number. This. And this poses a true challenge when communicating head to head clinical trial results despite being the preferred design from a clinical relevance point of view. And of course, we all know that placebo controlled trials are rarely if ever us a cutie in oncology due to the severity of the disease and hence why that is something that is rarely contemplated. If we go to the next slide, slide number 7. Another way to look at add on trials and head to head is to look at what is it you actually measure. If you look to the left on this slide, you see that in a head to head trial, you measure the delta between the two drugs. And of course, once again, if the comparator is highly relevant, such as in the case with pomalidomide, even if you have an amazingly good drug, the delta will be numerically smaller in absolutes than the additive effect you have in an add on trial where you add a drug. The slide to the in the box to the right, you see that drug B is relatively less efficacious than drug B in the head to head design, the additive effect will look numerically larger despite being the inferior drug. And I think this is a very, very important point the when interpreting results. Very few drugs in add on designs would ever reach anything else than inferiority in a head to head design. Very important point to realize. If we go to the next slide, slide number 8. Why did we go for a head to head design? Well, successful drugs in multiple myeloma all have labels that allow for single agent plus minor steroid use. And at this time when we initiated this trial, that we were not aware that we would get such great results in Horizon that that would support an accelerated approval. The while some argue that this is a triplet market, almost half of all the patients are still only receiving single agents plus steroids. The and there's a significant off label combination use, meaning that labels for single agent plusminus steroid is still the staple in the foundation the multiple myeloma market. And the reason for single agent and post steroid use such as the 2 drugs that are compared in Ocean the is because of tolerability, resistance development, comorbidities and refractory status. The the number of treatment options for these later line patients shrink to minimum very, very rapidly and there's a huge need for new treatment options. So we actually had a choice back in 2016 to either go head to head with lenalidomide, the Bortezomib or pomalidomide. And the choice was simple, because pomalidomide was the de facto standard of care already then the data in the later lines, which is where you start when you try to build the clinical database for a new drug. If we go to Slide number 9, you can see the various outcomes that the head to head comparison can give. Either you're superior, which means that your point estimate with the standard error bars are all below 1, the it means that you're somewhere around the middle mark with some standard errors predefined that you have predefined together with regulatory authorities. And of course, if you're far to the right, you would finally be inferior. What does these two results mean? And I think this is very important when we go to Slide 10. So any drug you test has a true treatment effect. We don't know it, but there is one. That is the true an absolute treatment effect of any given medicine and an indication. And when you do a trial and you compare it to something, the true treatment effect can either be worse, same or better than your comparator. The problem is that you don't know the true treatment effect. You approach your clinical trial database with statistics and you try to either verify or exclude under certain conditions certain outcomes. What non inferiority means is you have excluded under certain conditions that your drug isn't worse. So it's either same or better them your comparator, but you can't say whether it's same or better. The only thing you can say from a statistical point of view is that you have excluded that it's worse. And of course, if you go to the next slide, Slide 11, the only difference between non inferiority and superiority is that now with a superiority outcome, you have also excluded that you're the same. Of course, under statistical boundaries that you have predetermined together with the regulatory authorities. But ultimately, they are more similar than one might think in terms of real clinical outcome. So with that being said, before we go into the results section, we go to Slide 12 And just look at the market shares in relapsedrefractory multiple myeloma in the U. S. In 2020. The Pomalidomide is still the largest drug. And please note that the total market share here can be larger than 100% because there's a lot of combination use as well. And as you can see, given that we have gone head to head with this drug, the it also means that we have gotten data with nelsleuthen where we can compare it with the key reference in RRMM for both safety and efficacy. The database is a treasure trove to understand moleslufen. With that, I would like to bring the word to our Chief Medical Officer, Claus Bakker, to go through the results. Claus? Thank you, Jakub, and good morning, everyone. The presentation. Before I start, I just want to share on a personal note that today you hear a very, a very satisfied CMO who is really pleased with the results. And I'm excited to be able to share these results, these top line results with you today. Let's start now at Slide number 14. So the COSION study. And Jacob touched upon it already a couple of times. But this is a trial where we have included multiple multiple myeloma patients who have failed 2 to 4 prior lines of therapy, including being refractory to lenalidomide the clinical trial within 18 months or have progressed on lenalidomide within 60 days of randomization. We enrolled 4 95 patients the randomized way, 1 to 1, with the primary endpoint being PFS and key secondary endpoints being overall response rate an overall survival. This was a global study with over 100 participating sites in 21 countries. A true global study with a huge impact. If we now go to Slide number 15, the details of the future. To the left, we have the earlier years to the right, we are in the future. The next question. So it is already almost 4 years ago that the first patient was treated in Ocean in June 14, 2017. Then the results that we're complete in terms of enrollment of the 450 initially planned patients. The however, to our positive surprise, we saw that patients stayed on treatment longer the benefit, basically saying that they were benefiting from the drug more than we had anticipated on average. The study. This made us decide to over recruit a little bit to 4 95 patients, which made the study fully recruited the full year of September 2020. Then in March 2021, we reached the number of events for our primary endpoint. The results. And here we are today at May 25 to disclose our top line results. And of course, and we'll talk more about that in a minute, the presentation. We will also talk about our planning with regards to a publication and the presentation of the data at a future scientific conference. The results and we'll also talk about our regulatory interaction. Let's go to the results on Slide number 16. This. This is the result for the primary endpoint being progression free survival. And before I start, I just want to go back to what Jacob the set where you have an equal drug when you are at a hazard ratio of 1 in a head to head study. The results. If you look at the hazard ratio that we present here today, both by the independent review committee the investigator test results. We have a hazard ratio of approximately 0.8, the next question, which means that across the intent to treat population to full population, nalcfen performed better the P values differ, but this means that the result is the results so close between independent review committee and the investigator assessed result that it is really important to note that the regulatory authority will do its own assessment and look at the individual patient data. The and when you actually realize that we are so close to being superior on IRC, the totality of the data becomes important. The and when I speak about the totality of the data, I cannot share everything today. But we as a company believe, the results that we have seen so far that our total package is very strong. The safety of our customers. It's not only the hazard ratio of the primary endpoint, but also other endpoints where we are very confident that we have a good package to submit the regulatory authorities. And please note that when we talk about the improvement of median PFS, we talk about a 40% addition in a head to head trial. Almost everyone would be really pleased to see this in a add on trial. It would be great. The and here we see it in a head to head trial where we almost are above 40% the competitive needed PFS improvement. That's huge, either being non inferiority or superiority. It's very close, the but it is a huge advantage for Naflutin over Oma Little Mine. We also choose to share the overall response rate today. The why is that important? It is important because that tells you if the patient responds to the treatment and what can you tell as a physician the patient who comes for his or her first response assessment. And this is where we, with a doublet, are solidly above the 30% mark, the results, which is a really good result. And this actually means if you especially when you compare it for formalithomide that in terms of the doublet, the response rate is substantially higher for mafluthen when compared to formalidomide. The efficacy results, which we hope to share at a later scientific meeting, we feel that the outcome of this trial this very, very positive. Go to the next slide, please. The safety summary. The most physicians, and we know this from market research, would have anticipated that nalpluzent would do worse in terms of safety. The. Pomelemyde is perceived as a very well tolerated drug. It's used very often, as you could see from the market share numbers. The safety and we compare it between the two drugs that we had, 1, no new signals for naltlutuzan. So the safety profile with a number with a relatively high number of hematological adverse events, the we call them lab value abnormalities or paper talks was in line with what we know from previous studies. No new safety signals were identified the hematological adverse events could be managed clinically very well. What we also could see is that despite the fact that we had more neutropenias as part of the hematological toxicity. Comalidomide actually more infections than melatonin. And this was a surprise to us. More hematological toxicity on paper, the ultimate goal of the study, but ultimately less Grade 3 or 4 infections than pulmonelomide. In terms of non hematological toxicities, the other than infections, we had similar results when compared to formalidomide, which is very encouraging. And then the last point, the which I like to focus on is the discontinuation rate, because this tells you something about the tolerability of the drug. Pomalidomide is an oral the drug, and it is perceived to be very well tolerated. Joflutin is an intravenous drug. Despite that, the we have similar discontinuation rates for adverse events for both drugs being very, very reasonable. So we were very pleased to see this, that we were on par from a safety perspective with Poma Ledomike. If we go to the next slide, Slide number 18. This is about next steps. This. And what does this result mean for engaging FDA? Well, of course, we are currently in the process us with engaging the FDA on the OCA data. We will present data at a key scientific conference as soon as possible, the publication work has already started because we believe we have such a good result, we want to share this with the outside world the data as soon as possible. And that speaks to the confidence we have in our data that we want to progress this as soon as possible. The data we plan to file for supplementary NDA in the Q4 of this year. The in light of the OCEAN trial results, which we believe are very strong, we plan to ask for 2 things: 1, a label change the 2, also a full approval for COPEXO as a requirement for the accelerated approval. And we think the confidence that we are in a good position to fulfill both based on the totality of the data again. And in the meantime, the before I hand over to Marty, we of course continue and focus on our commercialization efforts with COPEXTO in the United States. The full approval. Now I'd like to hand over to our CEO, Marty Duvall, the we will take you through some further commercialization thoughts. Marty, over to you. Thank you very much, this class. So I'll cover commercial opportunity and future plans. So if we flip over to Slide 20. The so the first critical thing when we work towards bringing a drug to market is to establish that we have single agent efficacy. That's absolutely critical. We did that with the Horizon trial. We did it in an area of high unmet need resulting in an accelerated approval in the U. S. Now with our clinical development program, Ocean and Lighthouse significantly and expand the opportunity. So in thinking about the OCEAN trial, we are proving that single agent efficacy combined with Dex through head to head against one of the most widely used drugs in the space. And what are the results of that? We see more patients responding as Plaut outlined and having a longer progression free survival than the most widely used drug. So as it relates to Ocean, it's the head to head with pomalidomide, dollars 3,100,000,000 20 percent growth. We know that approximately $600,000,000 utilization in the U. S. Is attributed to the Palmdex combination alone and that the OCEAN trial and the results here provide the opportunity for us to move up in line of therapy to 3rd line and greater setting. So we certainly look forward to those interactions with regulatory bodies and sharing this data with physicians. The next step here that further links our trials and clinical development program with the fastest and largest growing drugs in the space. We have the Lighthouse trial, very important combination with DARZALEX. Again, another $600,000,000 in Palmdex sales in the U. S. Are tied to the triplet regimen, which adds Dara. So again, a fastest growing drug, one of the fastest growing drugs in the space and a significant opportunity for us as we know, besides showing that single agent efficacy, that combination use is very important in the space as we look to set ourselves as a foundational treatment. Moving to the next slide, I'd like to tie in also on 21, our COPAXONE commercialization strategy and why the OCEAN trial is so important to us becoming that foundational treatment. As we think about the utilization of products today, there's a domination of the image, the PIs, any CD38s and a recycling of old classes of drugs and a small use, but now growing use of drugs with new mechanisms of action. When we launched into this category and became or have become one of the agents here with the new mechanism of action, we are competing head to head with belantamab, selinexor, ide cel and others as a key agent here with the new mechanism of action. The but the second part of the strategy is to move away from this recycling of failed drug classes. That's exactly what the OCEAN trial shows, right? We have a lenalidomide refractory population where the randomization was to recycling the next image pomalidomide or use melflupin dex. And in this case, we showed a result that was significant versus that drug. So very exciting results the tie in and will help fuel our strategy and fuel the commercial uptake of COPAXONE in the United States and we believe around the world once we receive regulatory approval. Looking at Slide 2022, just to show some of the momentum from a pomalidomide perspective over the years. We see the growth on the left hand side of the slide of worldwide sales for pomalidomide reaching $3,100,000,000 as noted earlier $2,100,000,000 in the U. S. Alone with that 20% growth. And on the right hand side of the slide, we see that currently Palmdex and Palmdex combos the comprise 33% of the U. S. Share of patient market share according to intrinsic data. To a very significant commercial opportunity that is at our fingertips with our current clinical development program. Turning to Slide 23. So we see now the worldwide sales for DARZALEX on the far right hand side and it growing at 40%, a $4,200,000,000 drug. So we start with Ocean. This really sets a new bar with COPAXONE, positive head to head data, a strong efficacy profile for our drug as a doublet in 3rd and 4th line. Lighthouse will provide that first opportunity to expand our label with COPAXO being part of a triplet regimen in relapsed and refractory multiple myeloma. To really look forward to now our attention turn to accelerating accrual to the Lighthouse trial so that these results can also be made available. So flipping to the last slide. The best. And in summary, in June of 2017, we set out on a very bold mission to show that we could beat one of the best drugs in relapse refractory multiple myeloma. And we have a successful outcome with the OCEAN trial. Superior according to the investigators, non inferior, but right on the edge according to the independent review committee. The 40% higher median PFS is very important, will be important to clinicians who make decisions on which drug to choose to treat their patients. We believe that we're on this path to be a foundational treatment in relapsed or refractory multiple myeloma. We really look forward to the deeper dive and being able to share all the results, the totality of the evidence for COPAXO in the OCEAN trial at a conference as soon as possible and look forward to also in interacting with regulatory authorities and in particular the the FDA with a supplementary NDA that we have planned for Q4 of 2021. So before turning it over to the Q and A, I'd like to once again thank the patients, the investigators, the investors and the team that made this trial and the execution possible. So with that, I'll turn it back over to the moderator for the beginning of the Q and A session. The questions. Our first question comes from the line of Erik Huber from Carnegie. Please go ahead. Yes, hi. And first, I was going to some of my congratulations to a very solid Ocean Phase III data to the whole team. I have a few questions. First, given that the asset ratio was very close to fall the superiority bracket. As the progression free survival data continues to mature until submission in the Q4. Do you see a chance that we would actually turn out to get the liquidity ratio below 0.1 0.8, sorry. That's my first question. Then the second question. Secondly, could you comment on whether you had another look at the overall survival data and whether that is trending in favor of the Paxo. And finally also, if you could comment on the shape of the production free survival curve the separation of curves and whether the difference is also in favor of CapEx doing the tail of the curve. Thank you. Thank you, Eric, and we really appreciate your congratulations on the trial. So I'll turn it over to Klas to address the points on the hazard ratio being close, early look at overall survival and the shape of the curves. Good. Thank you. And more than happy to answer the questions. Us. So first, about an updated TFH figure in the future. We believe, this. But this is, of course, not something we know, but we believe based on what we see that there is a good chance that the PFS the signatures will go to a headwind ratio below 0.8. So we are confident that in a potential a data cut. This will become visible. Whether this will be used in regulatory interactions is, of course, a review issue, that we feel confident that it may turn that way. 2nd question, overall survival. The overall survival is not mature yet. So we cannot draw any conclusions also because the trial was not powered for overall survival. The study. And as you know, there are a lot of subsequent treatments available. So there is always a watering down effect in overall survival. The at this stage, I cannot say whether it's going in one of the other direction, but we the strongly feel that the overall survival supports the data that we see in the progression free survival. The strength of the PFS curve. And I'm happy that you asked that question because if you think about the PFS, the I can disclose that the curve does not look strange. The curve looks like a very light the PFS curves where you see a split that continues, no crossing of the lines and nice white space in between the curves. I think that's all I can share at this stage. But needless to say that I'm very, very confidence at our data looking at the shape of the PFS curve. I hope that answers your question. Yes, it did. Thanks a lot and congratulations to the data. Thanks, Eric. The And the next question comes from the line of Peter Welford from Jefferies. Please go ahead. The Hi. Thanks so much for taking my question. So just continuing in a similar vein. Firstly, just with regards to the patients in the study, I wonder if you could comment how many patients are still on treatment at this point in time in the study. Secondly, then just with regards us to the enrollment. Clearly, the study will be 10% over enrolled. I guess, could you make any comments at all, given the design for hazard ratio of 0.80. But clearly, the study was over enrolled. So I guess, clearly, the number of events the still as originally anticipated. But can you comment at all how many events were in this analysis that you're presenting? The I guess, I would have thought it would be over enrollment. The p value could potentially have been smaller. But if you comment on the number of events the that would be helpful. And then third, just on subgroups, I wonder if I appreciate it's early days, but any comments at the moment at all on any interesting subgroups or any signs that you see within the subgroup analysis. Thank you. The thank you, Peter. And again, I'll turn it over to Klas for comments on your questions. Yes. And I'd like to start with the question about enrollment. We did over recruit, but we were not changing the number of events that were needed for the study. So this data cut that we saw was aimed the 3 39 event. And I can tell you that the number of events was somewhat above the 3 39 events, but still very close, the same exact same as we would have planned for. So this over recruitment made us actually the number of events somewhat earlier, but the whole analysis is still the same and there should be no difference the number of patients still on treatment. We have about 70 patients still on treatment distributed across both arms. On the subgroups, that's a very interesting question. And if you can imagine that if you have a result that is so close us to superiority that you will have subgroups where we clearly pass the hurdle of superiority and are superior. The results. And although it's early days, as you mentioned, I think when I mentioned that we are very confident in this data, when we look at the totality of the data that, that is also driven by the strong results of PIPEXO in some of the key subgroups. So looking at subgroups, yes, the footprint of this drug in the clinical treatment landscape of multiple myeloma in the relapsedrefractory setting. So we are basically what I'm saying is that we are very encouraged by what we're seeing in some of the most important subgroups as well. I hope that answers your question. And the next the This question comes from the line of Patrick Ling from DNB Markets. Please go ahead. Yes. Thank you, guys. Could I ask, I mean, when you started this trial, you had one of the preconditions that the patient should have the chain lenalidomide pretty soon before entering the trial and then you relax those inclusion criteria. Did you see actually any difference in the patient's outcome whether they were very, very Soon that they failed LEN very rapidly before entering this trial or if it took some longer time since they had the Franklin launch. Yes. Hey, Patrick. Thanks for the question. I'll turn this one over to either Jacob or Klas regarding this change. Yes. I'm happy to start there. I think Patrick, very relevant question. To start with, I can say that the vast majority. And then I'm talking about 90% of patients had lenalidomide at their last line of treatment. So it's only a very small group the we're talking about. We have not done the analysis yet to see if there are any differences in between those patient groups. But looking at the totality of the data in the inclusion. We feel that the protocol change did not have a material impact on the study data. So the relaxation of the inclusion criteria did not lead to a relative over recruitment of patients that failed LEMS longer ago. So we couldn't see that trend back in the data. Jacob, is there anything you want to add there? No. I think you said it all, Claus, and we're going to do further analysis and look at both the duration of LEND treatment as well as the time point. Us, but ultimately, it's a very homogeneous population in terms of time points. So there might be something on duration. Okay. So just so I understand correctly, around 90% of patients failed lenalidomide within 60 days of entering the trial Because 100% of patients are LEN sailors. Yes. You could take that as a reference point. Yes. Okay, great. Then my second question, I mean, when you talk about scientific meetings, do you have any feeling for when you could present something? Our goal is to do it as soon as possible. And we need to do some more analysis to make sure that we present a full and clear picture of the results. But clearly, I think we may perhaps like the second half of Q3 of this year. I think that's still the base case, but we are looking into opportunities to do it even faster, given that we think we have a truly good result to share with the scientific community. Okay, great. Then last question. When you evaluated the patients now in the trial, Did you have to do any corrections or amendments for some sort of impact from COVID-nineteen? Yes. That's all I can ask. Good question. So COVID-nineteen has played a role the necessary sensitivity analysis and I can say that it did not it seems the it seems that COVID-nineteen did not materially impact the result or the quality of the trial. The study. So it's a very robust trial where COVID did not have a significant impact in terms of the results. Of course, in terms of the execution of the study, it was sometimes hard, especially last year to enroll in the right number of patients, but it didn't swing the results in any direction. So no material impact of COVID. Okay, great. Thank you, guys. The next question comes from the line of Andreas Brupbender from Medical Strategy. Please go ahead. Hello. Thanks for taking my question. It's rather naive when you think about the data regarding Quebec. So the you see it's definitely non inferior to Promalix and you just scraped the border to superiority. The safety signals were similar, you said. When you think about the commercialization, the what do you think why would doctors prefer PIPAXO over POMALYX? Thank you. Yes, it's a good question. Well, every I think this comes to it can come down to subsets, particular patient characteristics. I think in the case here, what we're seeing is a higher overall response rate. We're seeing a stronger progression free survival. We're seeing a regimen that is used once a month and is an IV formulation. In a lot of cases, the management of older patients. And let's think about the population that we're talking about here, taking a pill on a daily basis and relying on a patient to remember to take a pill on a daily basis is much different than the compliance you know you get as a physician in controlling that point of care by having them come in every once a month and receive their dose of COPAXONE. So I think it's those factors help to drive the choice of regimen. And again, here being on the border of a superior and equivalent result. We're thinking more bullish about what we've illustrated and believe that there'll be many situations in which COPAXONE would be selected over pomalidomide based on the results here. So stay tuned for more details regarding the subsets and additional full body of evidence from the trial. Awesome. Thanks. Could I add something there, Marty? Is that okay? Absolutely. Yes. I think also the the as you know, the relapsed refractory multiple myeloma market is very fragmented, but pomalidomide is seen as the best drug there is for these patients. And the fragmentation stems from all these comorbidities, refractory status, tolerability issues, etcetera, that these patients have. So it is a bit of an illusion to say that all these patients have so many options because in reality they don't. So regardless of the real statistical outcome here in the end, even though we feel strongly that we'll see what this ends up as ultimately in the eye of the regulators, right, that there is a huge group of patients for whom PAM is not an option. It is considered the strongest the performing drug in this segment. And we are clearly same or better than pumps. That's a solid position. And Jacob, it's Claus here. I would also like to add one thing that I haven't mentioned yet. We have shared this data with some of the investigators on the trial to get their perspective. And I can only say that they were the highly interest by the data, looking at the curve, some other detail. And I think going back to the question, why do you think that we could replace Omelisk us in the market. I think the early signals that we have gotten from physicians on the study who have seen the results are very encouraging. Thank you. Thank you very much. The next this. This question comes from the line of Rene Rauters from Kempen. Please go ahead. Hi, guys. And hi, team. Thanks for taking my questions as well. Just wanted to confirm that there are no major or key differences in patient characteristics between the arms of the trials. Marty? Yes, that is the case, Renee. Yes, please expand upon that class. No, I think we have the short answer is no. It's very well balanced trial, as you would expect with a randomized trial here, but we were pleased to see a very well balanced the study between both arms. Okay. And then second question, please. So can you remind us about the filing strategy in Europe and how these data fit in there? Of course. Absolutely, yes. I'll let Klotz comment on the regulatory cadence here. The Yes. So for the U. S, it's pretty straightforward. We will file for an sNDA later this year, and we believe we have a strong case based on the totality of the data to one get full approval, but also to get a label update hopefully to earlier lines of treatment. When it comes to the EU filing strategy. This study is intended to be used as a confirmatory study the of our Horizon trial, which is currently under review for conditional approval in the EU. The next question. So that's in short our strategy when it comes from a regulatory point of view. So it will be used for both the opportunities. Okay. Thanks very much and congratulations on the results. Thank you very much, Rene. The The next question comes from the line of Christopher Udi from SEB. Please go ahead. Hi, there. Thank you for taking my question. So when I turn this around, I guess there's sort of an outside chance of turning this into a the superiority demonstration. But I guess as it stands, when you've got non inferiority, is what you've demonstrated. How do you see this affecting your ability to get reimbursement, particularly in the EU and to get reimbursement in the U. S. In earlier lines of therapy. I guess Bristol Myers is going to be lobbying KOLs pretty hard to the strength of the language on in any guidelines. How do you see, I mean, you're David against 4 Goliaths us currently with a bunch of other mechanisms. I mean, I guess a score of drugs in development coming up behind you. So is the risk is there a risk that you get squeezed at the back end and are unable to penetrate earlier lines of therapy. I guess that's my question. Thanks. Yes. So maybe I'll start off just thinking about the U. S. I I mean, the current label is after 4 prior lines. So we're pushed pretty far back. And thanks for the question, Chris. Really appreciate it. The we're pushed into the area of high unmedical need based on the products that are available today. So that pushes us back to 5th line plus. Clearly based on the OCEAN trial, we're looking at 3rd and 4th line patients. So this is a significantly larger patient population. Would not anticipate there to be much challenge at all regarding guidelines and the authorities on those guidelines to widen the scope as it relates to Paco based on this extremely strong evidence and direct head to head comparison versus palmelitomide. We think the totality of the evidence from a regulatory fact that it's going to be strong, but I'll turn back to what Claus was saying regarding clinician reaction. Again, and it's early days, right. We just have these data now. And certainly, I think we'll see this play out even greater as we're able to present this data to more clinicians and they're exposed to it in a peer to peer setting. But we believe that they'll be highly motivated to select our drug. So from a reimbursement perspective in the U. S, don't see any challenges. Us from a regulatory or reimbursement perspective in Europe. Of course, it's kind of early days to begin thinking about that. Certainly pomalidomide is a widely used drug in Europe as well and it's a drug that has us a pretty decent price point as it relates to it. So being able to obtain a price points similar to pomalidomide would be excellent and then driving we believe the data then will stand on its own regarding our ability as Jacob and Klas have articulated into a patient population that has very different needs. It's very much a not one drug is not appropriate for every single patient. We believe that the totality of the data from the OCEAN trial opens up many opportunities for COPAXONE to be a very significant and foundational treatment in relapse and refractory multiple myeloma independent of the geography. Maybe I'll also turn that back to Klas and Jacob for their comments and thoughts. I think you said it all, Marty. I think one comment on the EU strategy where a non inferiority result would stand regardless on its own. And I think the fact that we're so close to superiority will make us having a stronger case. The. Needless to say that, of course, we are finding strategy in Europe is first focused on Horizon, which will be the starting point for our reimbursement discussions where OCEAN will be the new test, a confirmatory trial. But right now, I don't see any true impact of the OCEAN trial on the planned reimbursement strategy for Europe. Okay. So you mean that so I mean, in general, when we have new cancer drugs coming on to the market and trying to go head to head with an incumbent, particularly a very well entrenched incumbent with vast resources. That we typically see that they have to have a lower price. Can you elaborate on why you don't believe that would be the case here in myeloma. Could I just Well, I'd Mark. Sure. The sorry, yes, it's not on the price as such, Christoph. And I think that your questions are really well put, this. But I think you need to look at the activity of the drug for these patients. In add on trials in relapsedrefractory multiple myeloma, the average the asset ratio is around 0.65 and they include palm decks at the bottom. If you translate that, that means that you're adding half the units of POM in activity for these patients. That's your treatment effect, half of POM. We have a hazard ratio of 0.8, statistically non inferior. But if you look at the point estimate, we are adding 1.2 units of pharma activity to these patients. And that is ultimately the bucket of activity that we need to price. So I think in a way, you're a little bit stuck in the framework of add on trials when interpreting the the ratio here. And obviously, this will be an in-depth discussion, but the activity level we have shown for these patients It is a very steep mountain to climb and we have really over delivered and I need to stress that. Martin, sorry for that, just your point, sorry. Yes. No, thank you. Thank you for that. Also, Chris, in the only market that we have the drug currently available. When we looked at the landscape and pricing, approved as a triple class refractory agent and relapse refractory multiple myeloma. We looked at the price points for the 2 most recent entries and in particular that was selinexor and belantamab at the time and of course, i2Cel has since launched Surebeccma at a way different price point. But we price with the future in mind and with our vision in mind. We price with a vision that this OCEAN trial would be the success that we see it as today. So we priced with pomalidomide as a reference point. So from that standpoint, we've kind of taken that into account. We feel very confident in both the pricing, the benefit risk profile and our future opportunities related to COPAXONE uptake and commercialization. Look, we're out there in the market today as are others with data that is not robust head to head data, that is not data head to head against the most widely used drug. This is a very significant opportunity from a commercialization perspective when you show these kind of results. As it relates to Europe, I mean, there's still again, it's work in progress. We're early days. We're a day removed from having this top line data. As you know, our pressures are to get it out as soon as possible. There's a lot of work to be done on understanding the full data set. But again, we believe the totality of the data provides will provide for a very robust this opportunity in Europe and other geographies. Okay. Thank you very much. And we have a follow-up question from the line of Peter Welford from Jefferies. Please go ahead. Yes, thanks. So just very briefly, just with regards to the FDA, just so I can understand here the different scenarios here. Is it does the full approval scenario, with regards to that, does that necessitate getting ocean data on the label? So I guess what I'm saying is, are we really saying here that do ocean data get on the label like a new label indication? Or do they get on the label as just in the clinical data section? Is one of those required for full approval? Or can this convert to full approval With no mention of ocean data, because the FDA doesn't regard this trial as a success to put on the label, but there is still a conversion the full approval scenario. Thank you. Yes. Good question, Peter. And I believe one of the potential outcomes and we believe that it's the ultimate outcome could be a full approval with the data not being in the label. Obviously, as Klas mentioned, we believe that the totality of the data and the results here support a full approval and inclusion of the OCEAN data set an expansion of the indication into earlier lines of therapy. And that's what we will be seeking, but there is a case where what you're describing could happen. Klas, any further thoughts and reflections on that? Yes, I think you said it well, Marty. Of course, we don't have a crystal ball, but based on the totality of the data. Again, I cannot stress enough how much we are looking forward to share the data at a scientific meeting. I think we have a very, very good shot at also changing the indication based on the OCEAN trial. Of course, I have to put a disclaimer there because we don't know. But based on the totality of the data and what we hear from KOLs, but also from our regulatory people, we feel confident that we have a good chance there. Thank you. Can you just give a last thank you also, the Peter, and that is it's 2 separate processes, the confirmation and the label. They are, of course, merged in terms of package, but the rules and regulations around them are separate. The confirmation requires randomized data. The label is of course the regular path. So it is actually technically 2 different topics. I'll ask Per your question. And we have just one more question from Patrick Ling from DNB Markets. Please go ahead. The Thank you. Just a short follow-up question. I mean, have you looked into where the physicians the assessment and the independent review committee assessment, where they differed and why they ended up in slightly different outcomes? That's a great one. I'll turn that over to Klotz and Jacob both the comments. Yes. The short answer is yes. We looked at these discrepancies. And it's not without a reason you have an IRC because they have an independent look at the data. The we believe that you will see as you saw, the results are very close, whether it's from an investigator, Seth Mazor and IRC. And there are always judgment calls the results where it's not easy to say one is right or one is wrong. And I think this is also important when we consider the fact that the the FDA will look at it from an individual patient level where it could go either way in being superior or not. But then again, regardless of where we land on superior or not, I think the totality of the data will still be the leading part of the discussions with the FDA. And given the tightness of the data, are we talking about many patients where the IRC and the physicians differed in their opinion? And as there are no further questions, I'll hand it back for any closing remarks. Thank you. And thanks to everyone for joining us this morning and digging in. Excellent, excellent questions. Just want to reiterate how proud we are of the data set, how excited we are to bring this forward to conferences first, this to clinicians and decision makers on prescribing prescribers the company and of course regulatory authorities. It will be will also be critical here. So we look forward to providing you updates on that. Again, thank you for your participation and look forward to talking to some of you very soon. The call. So thanks very much. Take care and have a good rest of the day. This concludes our conference call. Thank you all for attending. You may now disconnect your lines.