Hello, and welcome to the Oncopeptides audiocast press conference 2022. Throughout the call, all participants will be in a listen-only mode, and afterwards, there will be a question and answer session. 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 just a short moment on the front page of this presentation. Of course, the core topic of today is that the CHMP issues a positive opinion recommending full approval for Pepaxto in the European Union for patients with triple-class refractory multiple myeloma, which is really a big set of news and a milestone from Oncopeptides, as well as for these patients. Next slide, please. Of course, today, we're gonna 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 webpage afterwards. Next slide. Slide number three.
Today we have three participants from Oncopeptides that will talk and are available for Q&A during this session. It's myself, Dr. Klaas Bakker, our Chief Medical Officer, and Annika Muskantor, our Chief Financial Officer. Introduction. Let's go to slide number five. It's highly unusual to have a vision and mission statement in a webcast regarding a specific set of news such as today. 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 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.
Eventually today, EMA completely sees the data as we view it, and it feels very much like redemption to some extent because we were so questioned last year. That is why this statement is here, because this is about science, and it is about evidence-based medicine, ultimately. Next slide number six. I will very soon leave the word to Dr. Klaas Bakker. As stated, the core is that the CHMP recommends full approval, so not conditional for Pepaxto in Europe. Klaas.
Thank you, Jakob, and good morning, everyone. As Jakob mentioned, we're talking about a full approval. 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. This means a full approval. I will quickly jump to the last bullet because it is interlinked, which means also in this case, that there are no post-marketing commitments. This is very important because normally you can get a laundry list of additional studies that you need to perform, mostly on safety, but also sometimes efficacy.
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. By that time, in about 60 days, we are actually allowed to market the drug in Europe. That marketing authorization is valid in all EU member states, but also in European Economic Area countries, including Norway and Liechtenstein. Then the label, and this is very important. Slide seven, please. The Pepaxti label in EU.
An important slide since this is the patient population that is eligible for this drug right now. Important to mention is that this is primarily based on the phase II HORIZON study. That means that you have a slightly later patient population 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 three most often used drugs in multiple myeloma, a so-called proteasome inhibitor, PI, an immunomodulatory agent, an IMiD, and one CD38 monoclonal antibody. This is a huge group of patients with unmet needs. Once they have progressed through these classes, and almost all will, you basically have no standard of care left. Importantly, we have a label which speaks about at least three prior lines of therapy.
I want to call that out since the label that we initially had in the U.S. was four prior lines of treatment. 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 know that this is about 25%-30% of all patients, but also the time to progression should be at least three years from transplantation. 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 Pepaxto. Next slide, please. Slide number eight.
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. This makes this even more exciting because what the CHMP did 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 from the population in HORIZON that have had at least three prior lines of treatment and are triple-class refractory, and those patients who 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 BOSTON study, and you will 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. During those 2.3 months, they are already deriving benefit from our drug.
To the statement that is below from the press release. I know Jakob will talk more about that in a minute. 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 the 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. What you see that in this group of patients, which in real world comprises about 75%-80% of the patients, the blue line is melflufen and the red line is pomalidomide. You see that there is a nice and consistent split of the curves that starts early, around four to five months. Please note, this 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 II variation, where I will also speak to in a minute.
Keep this curve in mind when you think about Type II variation, which I will talk to in a minute. Next slide, please. There was a safety warning 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. 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. After that extensive review, the EMA concluded black on 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 USA.
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 three years. Importantly, this is not a safety issue. This is a group of patients where the benefit against Pomalidomide is somewhat more or less pronounced, hence it was taken into the indication statement. Very important is that the population that remains after you take out those patients who have had an early progression after stem cell transplant, is a very significant population. These patients are often the elderly with a lot of comorbidities who are non-transplanted anyway, and this is the group represents the largest group of relapsed refractory multiple myeloma.
This means that this group particularly benefits from treatment with Pepaxti. Bear in mind the curves that you have just seen here, because this is the population we're talking about. Next slide. This quote from our principal investigator with OCEAN is truly important. As Jakob started to say, this is very good news for patients, and we sincerely believe that is the case. With us, a lot of external experts who have supported us throughout the review with EMA. There is a high unmet medical need in relapsed refractory multiple myeloma. There are a lot of new treatments, but the vast majority of patients won't be eligible for those treatments. To have a once monthly infusion drug of only 30 minutes is just very convenient and important for physicians to have. The unmet need is there.
There is clearly a place for Pepaxti in the current treatment landscape. Next slide, please. Now, Jakob will start to talk you through this slide about what really actually happened in 2021, 2022. Jakob, please.
Thank you, Klaas. 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 ITT 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 a so-called forest plot. Normally these lines are aligned on it, on top of each other like a sandwich. 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 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 a case of true heterogeneity. That is, that both study drugs acts 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 melflufen 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. This is clearly EMA's position, which actually means that the information value 1.1 is dubious.
A stupid example is similar to if you take the average weight between an anorexic patient population and a morbidly obese patient population. That number doesn't tell you anything. You need to look at these two patient groups specifically to understand what is going on. When you have a significant true heterogeneity, you need to assess benefit risk for each patient group individually. Given 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 a prior transplant that was less successful. 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. I will leave the word to Klaas for the next slide number 14, about the regulatory path forward.
Thank you, Jakob. This is an, I cannot stress enough, very important message on this slide. Why? Because we still have a Type II variation, as it is called left. 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. OCEAN was originally designed for patients with two to four prior lines of treatment and being lenalidomide refractory. This is a huge population, early stages of relapsed refractory multiple myeloma. 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 II 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. On the Type II variation, as mentioned, it's two to four prior lines of treatment, not triple class refractory, and lenalidomide refractory. That's almost all patients when they are in a state of relapsed refractory multiple myeloma. That means that within Europe, we have the possibility to vastly expand the current label that we have. 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. market, and we did everything to maintain it. This is a product that is still approved. We have done all the formal regulatory and pharmacovigilance work to keep the application alive, so to say.
The moment we reach consensus with the FDA, this drug can be marketed again. All other things are maintained in the meantime. Now, 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 a so-called silent observer during the intense meetings with EMA we had in 2022. In the deciding CHMP meetings, as well as during the scientific advisory group meeting, we actually had the FDA listening in. This is important because that means that the FDA was able to listen to experts who all clearly state that this was a case of true heterogeneity.
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 six months. With that, I would like to hand back to Jakob Lindberg.
Slide number 15, thank you. Commercialization. This is, of course, a tricky topic given the past year. Fundamentally, we have, of course, advancing all our market access activities in Europe. In light of this, 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 gonna assess all commercialization options. Of course, this is a complex equation, both by, you know, the cost of capital, the business development interest, and exactly what we think we can achieve ourselves. We need to come back to this topic in detail during the second half of this year. 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. 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 standalone entity in the U.S., but need a partner there as well. 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 standalone launch in European countries in the sequence that we can do that.
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, thank you. Number 16. Of course, we are considering all financing options right now. We have a European Investment Bank loan facility. 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. Just to reflect our new situation, we hope to resolve that within short. We're 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.
We will come back with details once we have them. Slide number 17, thank you. That was a large section today about the European approval. 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. Let's go to slide number 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 or 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 treatments.
The point of this is just that this is a significant market opportunity, of course. If we go to the next slide number 19. These are just some numbers, so you understand the sizes of these markets. They are very sizable. 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. 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. That is what we should talk about on the next slide number 20.
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 metabolized 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 myelosuppression. It only adds to the safety profile of the drug. We can see no relationship to the efficacy. With OPD5, we have stopped the movement out of the warhead from the cell. 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. A clear next generation.
OPD5 is ready to enter the clinic, but of course, we have lacked the resources to actually do this. The plan would be to do a phase I/II trial with this improved construct in a basket trial in all these three disease areas to see both the optimal dose, of course, as well as to see the activity level. We have something on slide 21 that I think no one really expected us to have, but this is a biologic. This is a multivalent construct consisting of antibodies that work as an NK cell engager. 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.
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. They proliferate very easily. That is these are the T-cells that you 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 a vaccine knows this, and you feel pretty bad. 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 you're after.
The idea is here that with an NK cell engager, you get the benefits of the T-cell engagement, but with better safety profile, which is needed very much for this construct. We are not alone in this, but the pre-clinical data we have is really best in class. The reason for us disclosing something like this early is that there has been recent transactions in this field of significance. Hence, we feel the need to disclose that we actually have a construct of real pre-clinical value here. Even though as a clinical company, most people don't pay much attention to the pre-clinical 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.
If we do this the right way, we should be able to enter the clinic in 2024 with this construct. With that, I think we go to slide 22 and just conclude here. I believe we have a slide with conclusions 23, right? Yes. 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 were launching fourth quarter.
We will also plan to submit, like Klaas said, a Type II variation to also include the OCEAN population in our label to broaden it. We plan to send in the Type II variation to the European Medicines Agency in the fourth quarter of this year. We have intensified the FDA interactions, as Klaas stated, the FDA participated all along the way, and we hope to reach some sort of resolution in the second half. 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, the next slide.
Given our situation, we will of course have partnership discussions because we need to establish a business model and to maximize the value for you 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 unprecedented 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 the OCEAN actually showed 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 II variation based on OCEAN to EMA in the fourth quarter. Of course, we will now accelerate publication and scientific communication vis-à-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. 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.
Thank you. If you do wish to ask a question, please press zero one on your telephone keypad. If you wish to withdraw your question, you may do so by pressing zero two to cancel. Our first question comes from the line of Adam Karlsson from ABG. Please go ahead.
Hi. Thank you for taking my questions. I have a couple to begin with, firstly, congratulations on the approval. In the end, it comes down to the date, and it's uplifting to see that went through. I know you guys and you, Jakob, in particular, played an important part in this successful outcome. Congratulations. Well deserved. My first question is on dosing and toxicity. Something that came up as an issue with the FDA back in October when Pepaxto was withdrawn from the U.S. 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 aligns with the EMA's interpretation. The second part of that question, if a new dose-finding study was still needed, do you have any sense for the likely scope or size of that kind of study? Do you anticipate that could be run in parallel to the lifting of the clinical hold, or would it need to come before? 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, virtually sort of put in the same bucket and benched against the likes of Blenrep and Xpovio. As you mentioned in this presentation as well, these drugs haven't had particularly stellar launch trajectories. At the same time, though, Pepaxto now has the superior reading relative to pomalidomide in the on-label population. I wanted to get your thoughts on how material you think this data could prove and how you see Pepaxto managing to sort of distinguish itself in that triple-class refractory setting. Thank you.
Thank you. Thank you, Adam. I will take the second question first, and then I will leave the floor to Klaas to take your first question. First of all, competitiveness is a complex topic because these patients are very ill, they are elderly. 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 ease of use and the management of side effect profiles. 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 contain 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 now very good activity numbers in these triple-class refractory patients that stand up really well. 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, 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. 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, you know, 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 comes our, you know, slightly smaller organization today than what I would like, et cetera. From a data point of view, we have a really good starting position here. With that, I will just leave the word to Klaas to discuss the dose-finding question.
Thank you. 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. Back last year, when the overall survival hazard ratio of 1.1 was taken, as it was by the FDA, there must be a 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. What comes from that is that we have significant number of dose reductions with our drug. 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 one 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. 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 site-targeted small molecule as people know it. This is an alkylator, a cytotoxic agent. 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 to the maximum tolerated dose, which is the normal way of doing this. 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 dose regimen has now been concluded to be safe for patients.
To then out of the blue, start to talk about a 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, a new dose-finding trial should not be necessary from our point of view.
Thank you, Klaas. Just to add, Adam, one 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 40 mg monthly dose. To actually move these patients, 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. Given that pomalidomide standard of care, you can't just disregard such data in our opinion.
Great. No, that's very helpful. Thank you.
Thank you.
Just as a final reminder, if you do wish to ask a question, please press zero one on your telephone keypad now. We have another question from the line of Boris Peaker from Cowen. Please go ahead.
Great. Thank you for taking my question. First, I just wanna ask on the OCEAN trial. So, as you mentioned that it was used as safety database for the CHMP. I'm curious, what is the path forward if you ultimately wanted to get approval in the same setting than the OCEAN study was conducted, basically second line? What would be the path forward, let's say, in Europe for that label expansion?
Thank you, and good morning, Boris. That is the Type II variation. 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. You would then seek exactly the pomalidomide label because that is where the OCEAN study was conducted for patients, excluding patients with then a stem cell transplant with a time to progression less than 36 months post-transplant. You saw the overall survival curve for those patients from the OCEAN trial and of course the PFS. I think the hazard ratio is 0.55 or something like that, the hazard ratio.
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.
Just to clarify, that wouldn't be an analysis of existing data for this Type II variation. That would be rerunning the study. That's why I just wanted 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 just exclude patients with low benefit compared to pom, given the true heterogeneity of the trial. If you look, the guidelines here in Europe and in the U.S. are actually identical. If you look at the white paper published by the FDA last summer, this is sort of the type two 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.
Then you see that some subgroups have a hazard ratio on the OS that is above one, and you basically exclude them from the indication statement since it was a trial where the null hypothesis was satisfied. Sorry, Klaas will just add some comments there as well.
Yes. Good morning, Boris. I think it's good for this to refer to the PAOLA-1 study, which was the approval of Lynparza in ovarian cancer. We are in exactly the same situation. 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. I think that's the example that is most obvious here.
Got it.
Thank you.
My last question on publications. Can you maybe comment on any specific publication we should be expecting, or you're not aware of timeline and maybe a place?
I mean, the most important one is that based on this very thorough analysis and investigation together with EMA plus, you know, in a way, their conclusions here, of course, a big benefit-risk assessment where this heterogeneity is the focus and hence which patient groups that benefit and which groups that do not is probably from melflufen's perspective, the most important one near- term. Yes.
Great. Thank you for taking my question.
Thank you, Boris.
We have no further questions, so I'll hand it back to the speakers.
Thank you very much, and thank you for being here today. 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 diligent as we can. 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. 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.