Oncopeptides AB (publ) (ONCO) Earnings Call Transcript & Summary

Hello, and welcome to the Oncopeptides audiocast press conference 2022. [Operator Instructions] And today, I'm pleased to present CEO, Jakob Lindberg. Please begin the meeting.

Thank you very much. Warm welcome to this webcast at the back end of the news that we released Thursday. We'll stay at the short moment on the front page of this presentation. And of course, the core topic of today is that the CHMP issues is a positive opinion recommending full approval of Pepaxti in the European Union for patients with triple-class refractory multiple myeloma, which is really a big set of news and a milestone from peptides as well as for these patients. Next slide, please. Of course, today, we're going to do forward-looking statements. And for anyone that wants to know the particular details about the legal disclaimer, all the text is on this slide, and it is also available on our web page afterwards. Next slide. So Slide #3. Today, we have 3 participants from Oncopeptides that will talk and are available for Q&A during this session. It's myself. It is Dr. Klaas Bakker, our Chief Medical Officer; and Annika Muskantor, our Chief Financial Officer. So introduction. Let's go to Slide #5. It's highly unusual to have a vision and mission statements in the webcast regarding a specific set of news, such as today. But I think this still is very important to us because we have always said that science and data drives us, and that is why we are here today because the last year was quite peculiar for us. We strongly -- we took a very strong position regarding our data set in OCEAN. And as you know, this was questioned by the Food and Drug Administration in the U.S. But eventually, today, EMA completely seized the data as we view it, and it feels very much like redemption to some extent because we were so questioned last year. And that is why this statement is here because this is about science, and it is about the evidence-based medicine ultimately. Next slide, Slide #6. I will very soon leave the word to Dr. Klaas Bakker. But as stated, the core is that the CHMP recommends full approvals and not conditional of Pepaxti in European Union. Klaas?

Thank you, Jakob, and good morning, everyone. As Jakob mentioned, we're talking about the full approval. And what we mean by that is that we initially applied for a conditional marketing authorization, which means that another trial would have to follow and confirm the benefit risk. What has happened now is that EMA has considered OCEAN to be the confirmatory trial, which means that there was no other confirmatory trial needed for this drug. So this means a full approval. And that will quickly jump to the last bullet because it is interlinked, which means also in this case, there are no post-marketing commitments, and this is very important because normally, you can get a laundry list of additional studies that you need to perform, mostly in safety, but also sometimes efficacy. And in this case, beyond the normal pharmacovigilance, the European Medicines Agency has not given us any post-approval commitments, which ultimately means that we don't need to perform any other trial to have this product fully approved on the market. We are not approved yet. We have a positive opinion. And what that means is that we will get, with certainty, a formal marketing authorization by the European Commission approximately within 60 days. So by that time, in about 60 days, we are actually allowed to market the drug in Europe. And that marketing authorization is valid all EU member states, but also in European Economic Area countries, including Norway and Liechtenstein. Then the label. And this is very important. Slide 7, please. So the Pepaxti label in EU. An important slide since this is the patient population that is eligible for this drug right now. And important to mention is that this is primarily based on the Phase II HORIZON study. And that means that you have a slightly later patient population than we would have -- than what we have used in OCEAN, and I'll come back to that. Importantly, this is a label for triple-class refractory patients, which means that they are refractory to the 3 most often used drugs in multiple myeloma, the so-called proteasome inhibitor, PI; an immunomodulatory agent, an IMiD; and 1 CD38 monoclonal antibody. This is a huge group of patients with unmet need. Once they have progressed through these clauses and almost all will, you basically have no standard of care less -- left. And importantly, we have a label, which speaks about at least 3 prior lines of therapy. And I want to call that out since the label that we initially had in the U.S. was 4 prior lines of treatment. So this is an earlier line of treatment than the U.S. label, which means that there are more patients eligible at that stage for this drug. The last sentence says something about patients who have had an autologous stem cell transplantation. Important to note that this is about 25% to 30% of all patients, but also the time to progression should be at least 3 years from transplantation. And if you do the math there, you end up roughly with 20% of patients in these later lines that may not be eligible for our drug. That still means that the huge majority of patients at this stage of their disease will be eligible for treatment with Pepaxti. Next slide, please. Slide #8. As mentioned, the positive opinion is based on data from the HORIZON study, but very much supported by data from the randomized controlled Phase III OCEAN study. We will talk a little bit more about data. But importantly, OCEAN is used as a safety trial, so to say. And this mix is even more exciting because what the CHMP was basically rubber-stamping OCEAN as a study that confirmed the safety of using Pepaxto or Pepaxti in patients with triple-class refractory multiple myeloma. Next slide, please. So if we go to the results in the indicated population, so these are the numbers that are derived through the population in HORIZON that have had at least 3 prior lines of treatment and triple-class refractory and those patients that did not have an early failure after their autologous stem cell transplant. The overall response rate is 28.8%, which is high in this setting. If you look at competitors in this space like selinexor or belantamab, you will see numbers that are slightly less or in the case of belantamab the same. The duration of response, however, of 7.6 months is quite long for this advanced stage patient population. Also there, I invite you to look at the selinexor data in the [indiscernible] see that this is a very robust number at this stage of the disease. Also, the time to response, which is very important because it takes some time for a patient to respond to the treatment is 2.3 months. But during those 2.3 months, they are already deriving benefit from our drug. Then to the statement that is below from the press release. I know Jakob will talk more about that in a minute, but it basically talks about the OCEAN study and that OCEAN has a true heterogeneity, which is, of course, something that is very important. And Jakob will talk you through that later during the webcast. Next slide. Now this is an important slide, and I would like to spend some time on it to talk you through this slide. This is about OCEAN. So this is about the confirmatory study that was utilized by EMA. If you take out the patients who have had an early failure from their autologous stem cell transplant, this is the patients that you end up with. So this is the label population -- or not a label population, this is the population within the OCEAN study in patients who did not have a stem cell transplant or those who progressed more than 36 months after the transplant. And what you see that in this group patients, which in real world comprises about 75% to 80% of the patients, the blue line is melflufen and a red line is pomalidomide. You see that there is a nice and consistent split of the curves that starts early around 4 to 5 months. And please note, it is overall survival. This is not a progression-free survival, but an overall survival results slide, which means that in the indicated population, there is a benefit also in overall survival in the OCEAN study compared to pomalidomide. Very reassuring and this opens up for the so-called type 2 variation, where I will also speak to in a minute. But keep this curve in mind when you think about the type 2 variation, which I will talk to in a minute. Next slide, please. So there was a safety work in the U.S. on the overall survival result of the total population in OCEAN based on a hazard ratio of 1.1. It's always important to look at safety. And what EMA has done is an extensive review, and I can give some flavor to that. During this process that lasted for about a year, beyond our initial application, we received 260 questions. We sent over more than 400 documents. And after that extensive review, EMA concluded black and white, that there are no toxicological problems with our drug, which is very reassuring given the negative news that was out last year in the U.S.A. We now see confirmed that we don't have a toxicological safety issue with this drug, which has always been our understanding. Of course, we have those patients who benefit a little bit less and that are the patients with a prior autologous stem cell transplantation, where the time between transplantation and disease progression should be at least 3 years. Importantly, this is not a safety issue. This is a group of patients where the benefit against marizomib is somewhat more or less pronounced. Hence, it was taken into the indication state. Very important is that the population that remains after you take out these patients who have had an early progression after stem cell transplant is a very significant population. These patients are often elderly with a lot of comorbidities who are nontransplant anyway. And this is the group which represents the largest group of relapsed/refractory multiple myeloma. And this means that this group particularly benefits from treatment with Pepaxti. And then take in mind the curves that you have just seen here because this is the population we're talking about. And this quote from our principal investigator of OCEAN is truly important. As Jakob started to say this is very good news for patients and we sincerely believe that is the case. And with us a lot of external experts who have supported us throughout the review with EMA. There is the high unmet medical need in relapsed/refractory multiple myeloma. There are a lot of new treatments with the vast of patients won't be eligible for dose treatment. And to have a once monthly infusion drug for only 30 minutes is just a very convenient and important for physicians to have and the unmet need is there. So there is clearly a place for perplexity in the current treatment landscape. Next slide, please. Now Jakob will start to talk you through, this slide is more about what really actually happened in 2021, 2022. Jakob, please.

Thank you, Klaas. So I'll try to make this simple. This is really at the heart of the science and the controversy that surrounded the OCEAN trial. If we start to the left, we know that the primary endpoint of progression-free survival was met with superiority comparing melflufen plus dexamethasone head-to-head against pomalidomide plus dexamethasone. A highly relevant result given that pomalidomide is to the extent there is a standard of care drug in later line myeloma, the standard of care drug. It is the most used drug for these patients. However, the ICT overall survival hazard ratio was 1.1 indicated on the population level that there was a 10% increase in the risk of death on melflufen plus dexamethasone compared to pomalidomide plus dexamethasone. However, if you look at now you have the sample in the box in the middle, normally, this is a sort of a snapshot of the so-called forest plot. And normally, these lines are aligned on top of each other like a sandwich. And as you can see, this is clearly not the case here where they are very much driven apart. This means that in the study, we had significant heterogeneity in overall survival results depending on the patient population. This was something that took some time to decipher. This is highly statistically significant on the study level. Now when you have such heterogeneity and in this study, it is extreme. If you were to benchmark this study against other studies, the question is, is this just an observation that is, it could be a random finding, it could be something that could potentially be hypothesis-generating? Or is this a case of true heterogeneity? We argued strongly that this was the case of true heterogeneity. That is that both study drugs act exactly in accordance with how they have performed in previous studies. Now what happened with the FDA was that they said that this is just an observed heterogeneity. What are the implications of that? The implication is that the hazard ratio 1.1 is informative. That is the conclusion is that there's a 10% increased risk of death on the [indiscernible] treatment that consequently led to the safety alert and the clinical hold and everything that followed from that. However, since both study drugs behave exactly in accordance with previous trials, both drugs, it means this is a case of true heterogeneity. And this is clearly EMA position, which actually means that the information value of 1.1 is dubious. A stupid example is similar to if you take the average weight between an anorectic patient population and the morbid obese patient population. That number doesn't tell you anything. You need to look at these 2 patient groups specifically to understand what is going on. And when you have a significant heterogeneity that is true, you need to assess benefit risk for each patient group individually. Even that there was no toxicological safety signal, just like Klaas said, you then identify the patient population that benefits the least from treatment with melflufen, which, in this case, are patients with prior transplant that was less successful. And you exclude them from the indication statement, this is very clearly spelled out in guidelines. Interestingly, the guidelines here are identical in Europe and in the U.S. with regard to how this should be handled if this is a case of true heterogeneity. This was at the heart of last year's discussion, and that is why they also land in seemingly, so very different conclusions on how this should be handled. So I will leave the word to Klaas for the next slide, Slide #14, about the regulatory path forward.

Thank you, Jakob. And this is -- I cannot stress enough very important message on this slide. Why? Because we still have a type 2 variation as it is called, left. And what it means is that OCEAN, now that it is used as a confirmatory study, can also be used as a study to reach earlier lines of treatment. So OCEAN was originally designed for patients with 2 to 4 prior lines of treatment and being lenalidomide refractory. This is a huge population, early stages of relapsed/refractory multiple myeloma. And what we aim to do, is submit a package to EMA within the second half of this year, where we will hopefully successfully get this type 2 variation in.

Sorry, we just got information that it's the wrong slide from financial hearing. This should be Slide 14. I hope Slide 14 is now up. Sorry for that.

Thank you, Jakob. So on the type 2 variation, as mentioned, it's 2 to 4 prior lines of treatment, not triple-class refractory and lenalidomide refractory. That's it. Almost all patients when they are in the stage of relapsed/refractory multiple myeloma. And that means that within Europe, we have the possibility to vastly expand the current label that we have. So it is basically an enlargement of the group of patients that is eligible for treatment with Pepaxti. As mentioned earlier, the FDA interactions have intensified over the last couple of weeks specifically. Because, as you may know, we still have an approved product in the U.S. markets, and we did everything to maintain it. But this is a product that is still approved. We have done all of the formal regulatory and pharmacovigilance work to keep the application alive, so to say. So the moment we reach consensus with the FDA, this drug can be marketed, again, all other things are maintained in the meantime. Now how does the results -- how does it look like? How to resolve this situation? We can't speculate about that now. But what we can say is that we have a constructive dialogue with the FDA at this stage and that the FDA has also been the so-called silent observer during the intense meetings with EMA we had in 2022. So in the preceding CHMP meetings as well as during the scientific advisory group meeting, we think -- actually has the FDA listening in. And this is important because that means that the FDA was able to listen to experts where -- which also clearly states that this was against a true heterogeneity. So we look forward to the interactions with the FDA and we hope to resolve the situation in the U.S. now within the next couple of 6 months. With that, I would like to hand back to Jakob Lindberg.

So Slide #15, thank you, commercialization. So this is, of course, a tricky topic given the past year. But fundamentally, we have, of course, advancing all our market access activities in Europe in light of this. And we actually have kept the German team on the ground for a launch in Germany and the German-speaking countries in the fourth quarter. We're going to assess all commercialization options. And of course, this is a complex equation, both by the cost of capital, the business development interest and exactly what we think we can achieve ourselves. And we need to come back to this topic in detail during the second half of this year. But it's clear now that we have a real asset on our balance sheet in terms of the market authorization for Europe, and we'll see exactly what happens. When it comes to the U.S. situation, as Klaas mentioned, we hope to achieve some sort of resolution even though we have to come back to exactly what that looks like and what it pertains to in the second half of this year. And of course, that also plays a part exactly how we should commercialize this. I see it personally as highly unlikely that we would commercialize as a stand-alone entity in the U.S. but need a partner there as well. And so all these topics are actually interlinked. In the meantime, however, we fully go ahead with the market access programs for European launch, and we continue to prepare for a stand-alone launch in European countries in the sequence that we can do that. And the reason why we choose Germany first is because in Germany, you can start to sell a drug before you have the final price from the reimbursement agencies, which is different from most other European countries. Next slide, Slide #16. And of course, we have considered all financing options right now. We have a European investment bank loan facility. And as we have stated previously, we are in negotiations to change the tranche structure. The old tranche structure was put in place prior to all the events of last year and just to reflect our new situation. We hope to resolve that within short. But we are also, of course, looking at equity components because we need to strengthen the balance sheet, either through debt, through equity or both to actually successfully launch this product and make it available to patients. And we will come back with details once we have them. Slide #17, thank you. So that was a large section today about the European approval, but I think it's important to note and especially in light of this, what we have in the pipeline, we haven't talked about that much and we will just spend a very short moment on that. So let's go to Slide #18 first. These are the disease areas where we are active, right? We have multiple myeloma where we have Melflufen. Right now approved in Europe and the U.S., but we're not marketing in U.S. until we have resolved the situation with the FDA. We have pipeline of candidate drugs in both multiple myeloma, in lymphoma and in AML. These are diseases with a very large unmet medical need and large patient populations in need of better treatment. So the point of this is just that this is a significant market opportunity, of course. And if we go to the next slide, Slide #19. These are just some numbers so you understand the sizes of these markets. They are very sizable. So if you can provide patients benefit, you will make good business here as well. We focus on the patient, but ultimately, if you focus on the patient, that also result in shareholder value. What we have shown now to go to the bottom part of this statement is that our peptide drug conjugates are actually superior to the standard of care alkylators. And given that this platform now in Europe has proved to be valuable without any toxicological safety signal, this is something we need to continue to explore. And that is what we should talk about on the next slide, Slide #20. Because what we learned with melflufen from all the clinical data we have, is that as our PDC enters the cell and gets cleaved, right, or metabolize into portions, there is a leakage of the warhead, in this case, the alkylator back out into the system. This leakage only creates a safety signal. That is it creates not a signal, sorry, it creates myelosuppression. So it only adds to the safety profile of the drug. We can see no relationship to the efficacy. So with OPDC3, we have stopped the movement out of the warhead from the cells. So once it has entered in the cell, it stays there. Based on the clinical evidence, this is a clear improvement of profile where we will improve the safety with retained efficacy. So a clear next-generation. OPDC3 is ready to enter the clinic, but of course, we haven't -- we have lacked the resources to actually do this. And the plan would be to do a Phase I/II trial with this improved construct in a basket design in all these 3 disease areas to see both the optimal dose, of course, as well as to see the activity level. Then we have something on Slide 21 that I think no one really expected us to have, but this is a biologic. So this is a multivalent construct, consisting of antibodies that work as an NK-cell engager. So what is that? If you look in the area of clinical research and clinical development right now, you see a very large activity with something called T-cell engagers. You use the T cell to kill cells with a specific target. So you utilize the body's own immune system to kill the cancer cell. The challenge with working with T cells is that T cells are part of what is called your adaptive immune system. So they proliferate very easily that these are the -- T cells that we trigger with a vaccine, for example, or B cells, the adaptive immune system. When they get triggered and they proliferate, they release a lot of cytokines. Everyone with a severe reaction on the vaccine knows this, and -- feel pretty bad. But that is still pretty low in terms of side effect profile from what you can get in the clinic with these T-cell engagers. The idea behind NK-cell engagers is that NK cells do not cause this dramatic increase and hence, all the side effects, but they can still kill the target cell that we're after. So the idea is here that with an NK-cell engager, to get the benefits of the T-cell engagement, but with a better safety profile, which is needed very much for this construct. We are not alone in this, but the preclinical data we have is really best-in-class. And the reason for us disclosing something like this early is that there has been recent transactions in this field of significance. And hence, we feel a need to disclose that we actually have a construct of real preclinical value here. Even though, as a clinical company, most people don't pay much attention to the preclinical projects. We will come back with more information as we get it, but we are very excited about this, and we call it the SPiKE platform. And we -- if we do this the right way, we should be able to enter the clinic in 2024 with this cost. With that, I think we go to Slide 22 and just to conclude here. I believe we have a slide with conclusions, 23, right? Yes. So CHMP recommends full approval of Pepaxti in the European Union for patients with triple-class refractory multiple myeloma. We can formally market this once the European Commission has signed off on this recommendation, which will occur within 60 days normally. We are ready to launch in Q4 to start with the German-speaking countries. This will be valid in all European Union countries, including also the European Economic Area countries. I already stated that we will launch in the fourth quarter, we will also plan to submit by class set, type 2 variation to also include the OCEAN population in our label to broaden it. and we plan to send in the type 2 variation to the European Medicines Agency in the fourth quarter of this year. We have intensified the FDA interactions. And as Klaas stated, the FDA participated all along the way, and we hope to reach some sort of resolution in the second half. But right now, we don't know how that resolution looks, and we'll come back when we have more news to share on that. When it comes to near-term priorities, that is on Slide 24, next slide. We -- given our situation, we will, of course, have partnership discussions because we need to establish a business model and to maximize the value for your shareholders, we need to evaluate both stand-alone commercialization as well as partnerships in parallel. We will launch in Europe, and there are a lot of preparations to do that, and the activities are already ongoing for a fourth quarter launch. The FDA interactions, very important. This is actually highly [indiscernible] here. And I think it's both for the agencies and for us, it's important to reach some sort of common understanding on what did OCEAN actually show as a trial and what conclusions can be drawn from it. We'll come back in light of the full EMA approval once we have gone further in the FDA interactions, but they are already occurring. We will submit the type 2 variation based on OCEAN to EMA in the fourth quarter. And of course, we will now accelerate publication and scientific communication vis-a-vis the myeloma community. Given all the controversy that has been, it's very important that we share all the data, all analysis in a very open and transparent way for the peer review process to kick in appropriately. And hence, we will have publications, both in the third and the fourth quarter this year regarding multiple topics that we have today have touched very superficially on this investor call. With that, I leave the floor open for questions and answers. Thank you.

[Operator Instructions] Our first question comes from the line of Adam Karlsson from ABG.

I have a couple to begin with. But firstly, congratulations on the approval. In the end, it comes down to the data and its uplift you can see that went through. But I know you guys and you, Jakob, in particular, play an important part in this successful outcome. So congratulations, well deserved. My first question, though, is on dosing and toxicity, something that came up as an issue with the FDA back in October when Pepaxti was withdrawn from the U.S. So my question is, to what extent we should see that request for a new dose-finding study that came back in October? To what extent that should be seen as having come against the backdrop of that ITT OS safety signal, which may potentially come to be dropped then if the FDA lines for the AMA's interpretation? And the second part of that question, if a new dose-finding study was still needed, do you have any sense for the likely scope precise of that kind of study? And do you anticipate that, that could be run in parallel to the lifting of the clinical hold? Or would you need to come before. So that's the first question. I might jump to the second one straight away, if I could. The second one on commercial competitiveness, Pepaxto, was at least last year, post FDA approval, put in the same bucket and benched against like a [ blend rep and explore yields ] as you mentioned in this presentation as well. These drugs haven't had particularly seller launch trajectories. At the same time, the Pepaxto has disappear reading relative to pomalidomide in the on-label population. So I wanted to get your thoughts on how material you think this data could prove and how you see the packs are managing to sort of distinguish itself in that triple-class refractory setting?

Thank you. So thank you, Adam. I will take the second question first, and then I will leave the word to Klaas to take your first question. So first of all, competitiveness is a complex topic because these patients are very ill. They are elderly. So it is a basket of factors that create sort of the foundation for which drugs are used, where activity or efficacy is one, but also each of [ use ] on the management of side effect profiles. And we basically have a very easy-to-manage side effect profile because myelosuppression is something that every oncologist, especially hematologist, this is bread and butter. While the side effect profiles of both belantamab and selinexor contains some more difficult safety side effects, which are much harder to deal with, especially in an elderly population. In addition, if you then go to efficacy, we have, a, we have now very good activity numbers in these triple-class refractory patients that stand up really well. But on top of that, I think it's worth mentioning that with a successful OCEAN trial with a head-to-head superiority result compared to the most used drug in this segment, I would argue that we have the strongest empirical base right now to stand on in terms of benefit risk of the drug. So if you then take ease of use, very known material when it comes to the side effect profile and the strongest evidence base for benefit risk across patient populations, I think we have a very good chance. And once again, I mentioned evidence-based medicine, but on the criteria of evidence-based medicine to actually get a significant portion of use because the data supports that. Of course, we have to execute on that, and that there comes our slightly smaller organization today than what I would like, et cetera. But from a data point of view, we have a really good starting position here. And with that, I will just leave the word to Klaas to discuss the dose-finding questions.

Thank you, and it's a very good question, and I'm happy you actually bring this up here. This is very much intertwined with the safety profile of our drug. So back last year, when the overall survival hazard ratio of 1.1 was taken, as it was by the FDA, there must be kind of safety thing with this drug. That is what people start to think like this -- more people died on our drug versus the competitor drug. So what comes from that is that we have a significant number of dose reductions with our drug. And that is normal because that is how you actually treat a patient with chemotherapy. You go up to the maximum and then you titrate to the maximum tolerable dose. The EMA has the view that this is a very appropriate way of managing safety with these patients. That's also why the EMA has not brought up 1 single question, questioning the validity of the dose or whether it should be different because they have seen as we have observed as well that with this dose reduction schedule, you can treat patients very well without actually exposing them to additional risk because the number of clinical sequela from those cytopenias, as we call them, is very limited, almost no severe bleedings and no severe infections, or very limited at least. Then there is a second piece, and that is called Project Optimus in the United States, which is a flagship project from the FDA, where they aim to basically personalize medicine as much as possible, especially for the targeted small molecule therapies. This is not a targeted small molecule as people know it. This is an alkylator, a cytotoxic agent. And what we constantly hear back from physicians and experts in the field is that we should not lower our dose. We should give physicians the ability to treat the patients through a maximum tolerated dose, which is the normal way of doing this. So the way we look at this is that there should not be a new dose-finding study because we have a safe and efficacious dose that is established. We have more than 500 patients in our database when it comes to safety, all with the same dose regimen, that those regimen has now been concluded to be safe for patients. So to then out of the blue, start to talk about the new dose-finding study, while you have a very efficacious product with a good benefit risk profile on the market would seem a little bit odd to us at this stage. However, we cannot speculate what the FDA demands from us, but from a clinical scientific perspective, the new dose-finding trial should not be necessary from our point of view.

And just to add, Adam, 1 last point. And once again, this is evidence-based medicine. I think it's very easy given everything that happened last year to forget that what EMA actually sees in the OCEAN trial based on their assessment, seen as a confirmatory trial, is that for the vast majority of myeloma patients within the pomalidomide label, melflufen is a superior treatment alternative to pomalidomide, that is set with a [indiscernible] monthly dose. So to actually move these parts, then you basically invalidate that superiority result that, of course, from an evidence-based medicine point of view is extremely important. This is exactly how drug development should happen. And given that [indiscernible] standard of care, you can't just disregard such data in our opinion.

[Operator Instructions] We have another question from the line of Boris Peaker from Cowen.

First, I just want to ask on the OCEAN trial. So you mentioned that it was usually a safety database prior to the CHMP. I'm curious what is the path forward if you ultimately wanted to get approval in the same setting in the OCEAN study was conducted basically second line. What would be the path forward, let's say, in Europe for that label expansion?

So that is the type 2 variation. So we will then basically follow the exact line of reasoning in this approval, that is that patients with a less successful stem cell transplant should be excluded from the indication statement that is in line with the guidelines. And you would then seek exactly the pomalidomide label because that is where the OCEAN study was conducted for patients, excluding patients with a stem cell transplant or the time to progression less than 36 months post-transplant. And you saw the overall survival curve for those patients from the OCEAN trial and of course, the PFS, I think it has a ratio of 0.55 or something like that, the hazard ratio. So it's enormously beneficial for these patients compared to pomalidomide, which is, of course, once again, from an evidence-based medicine point of view, extremely important given that it's head-to-head with an active comparator.

But just to clarify, that wouldn't be an analysis of existing data for this type 2 variation, that would be rerunning the study. That's why I just want to clarify on that.

No, no, no. We would just use the OCEAN data set straight off because it is a study that met its primary endpoint of superiority and then you basically have to exclude patients with low benefit compared to pom given the true heterogeneity of the trial. And -- if you look, the guidelines here in Europe and the U.S. are actually identical. So if you look at the white paper published by the FDA last summer, this is sort of the type 2 cases that they list in that paper, where you have a significant heterogeneity that makes biological sense in line with the performance of the drug and the underlying biology and then you see that some subgroups have a hazard ratio on the OS that is above 1. And you basically exclude them from the indication statement since it was a trial where the null hypothesis was satisfied. Sorry, Klaas will add some comments there as well.

Yes. I think it's good for this to refer to the PAOLA-1 study, which was the approval of the Lynparza in ovarian cancer. We are in exactly the same situation. So if you look to the way how that label was handled, that is exactly the same situation as we are in, and we can utilize OCEAN for that. So I think that's the example that is most obvious here.

I had a question on publications. Can you maybe comment on any specific publication we should be expecting? Or you're not aware of a timeline and maybe place?

I mean the most important one is that based on this very thorough analysis and investigation together with EMA plus -- in a way their conclusions here, of course, a big benefit risk manuscript where this heterogeneity is the focus, and hence, which patient groups that benefit and which groups that do not, is probably from the [indiscernible] perspective, the most important one near-term. Yes.

And we have no further questions, so I'll hand it back to the speakers.

So thank you very much, and thank you for being here today, and thank you, Boris. This is very early for you. I'm sorry for the time. If any of you have any more questions, don't hesitate to contact us. We will try to answer them as diligently as we can. And otherwise, thank you for your continued support. This has been a very hard year for us, but ultimately, we seem to land in a good spot right now. And hopefully, we can resolve the FDA situation during the autumn given the science that we have behind us. Thank you very much, everyone, and have a great day. Thank you.

This concludes our conference call. Thank you all for attending. You may now disconnect your lines.