FDA Announcement

Mar 1, 2021

Slides

Thank you, operator, and thanks to everyone who has joined us for this call today. So despite the unusual hour here in Boston, I could not be more excited than to announce the approval of COPAXO by the FDA for the treatment of patients with triple class multiple myeloma COPAXO, there are times when a brand name and logo just sound, feel and look right and this is certainly the case for me here, a strong branding link to our company name and the drug, a name that sounds strong and enduring and a mark that links to our unique PDC platform and drug mechanism of action, I think it's safe to say that we are ready to fly. So on Slide 2, just to make a disclaimer here that please check our filings for fair balance and accuracy. And I'll move to Slide 3. So really excited to have the management team here on the line to participate. So joining me on the call today are Anders Martin Lauf, our Chief Financial Officer Doctor. Klotz Bacher, our Chief Medical Officer and Jacob Lindbergh, our Chief Scientific Officer. And a special note of congratulations to our former CEO and CSO whose vision, confidence, perseverance has led us to this milestone event. Way to go, Jacob. Thank you. Moving ahead to Slide 4, this is about a successful journey of innovation from discovery to commercialization. We at Oncopeptides have entered a space where some 80% to 90% of biotech companies fail to get. Our legacy team has pride in country and accomplishment for good reason. Now we move and aim to help patients. So as you know, the company was founded in Stockholm, Sweden in 2000 collaborations with the Upscale University, the Karolinska and Dana Farber and we continue to have and cultivate these foundational roots between stock home in Boston and we are transforming into a global curtailed biotech company. As we look at the timeline on the bottom, I set your sights to the Horizon trial and its initiation in December of 2016. Interestingly enough, this was a couple of months before the IPO and was seen as news flow from an investor perspective post IPO as when the OCEAN trial was initiated in June of 2017, it was designated to be the trial that would get us over the regulatory line. While Horizon delivered and delivered early and we're still pleased that we're able to bring our drug to patients probably more than a year earlier than we would have otherwise with the launch of COPAXO here in March of 2021. But that doesn't take away either from the significance of that OCEAN trial with top line data as we all know expected in Q2 of 2021. Moving on to Slide 5. So it's the Verizon study that underpins the FDA approval of COPAXO and as we know it was published in the Journal of Clinical Oncology in December of 2020. And there was also a letter to the editor and another note in the subsequent issue of the Journal of Clinical Oncology. So we're really proud of the RISE in trial and what it's meant to the development of our drug and to the commentary in the JCL. You see the inclusion criteria and just a reminder on the patient information, 157 patients, median age of 65, 5 prior lines of therapy and an extremely challenged patient pool in need of a therapy to provide them hope, 76% triple class refractory, 59% refractory to prior alkylator therapy and 35%, the largest plever who suffer from extramedullary disease or EMD. Moving on to Slide 6. So how did COPAXO perform? So here is a summary of the top line results for COPAXO in these patients with heavily treat pretreated relapsed and refractory multiple myeloma. In the intent to treat population, we see an overall response rate of 29%, a clinical benefit rate of 45% and an additional 24% of patients with stable disease, median duration of response was 5.5 months, median PFS of 4.2 months and an overall survival of 11.6 months with as we know grade 3 and 4 treatment emergent adverse events in the cytopenia area. In the triple class refractory patient population from Verizon of 119 continued the strong response rate, clinical benefit rate and stable disease rate and this also holds true for this large subset of 55 patients in the EMD setting, again, the highest unmet need in multiple myeloma and we believe to be the highest representation of these patients in a clinical trial. Moving ahead to Slide 7. So the FDA grants accelerated approval for COPAXONE relapsedrefractory multiple myeloma, we're pleased this is the first anticancer peptide drug conjugate and the words here on the slide are directly from our mechanism of action section in the package insert and we believe that this confirms the thesis of our platform, reinforces the differentiation of COPAXO versus alkylating agents and other agents that are either approved or in development for the treatment of multiple myeloma. So we've got the section here on the lipophilicity and the fact that we're enzymatically hydrolyzed. So this supports that selectivity to the myeloma cells, leveraging or targeting the immuno peptidases that we know are highly expressed in myeloma cells. We're really appreciative of the fact that the FDA has called out the cross linking of DNA is involved. This invites our continued research to fully understand and appreciate what differentiates COPAXO from all other drugs. We are really pleased with the connotion of a powerful anticancer activity through this inhibited proliferation and induced apoptosis of the tumor cells and the differentiation at the bottom on our synergistic cytotoxicity in melphalan resistant and non resistant multiple myeloma cells. Moving forward to Slide 8. So the accelerated approval of COPAXO validates our product unique benefit risk profile and positive impact on patients with high unmet need, the product is launching at least a year earlier than it would have otherwise had it been based on the OCEAN Phase 3 trial. This is great news for all of our stakeholders, patients, healthcare professionals, shareholders and employees. So importantly, this FDA approval is based on a subset of the horizon study. So among those triple class refractory patients mentioned on the prior slide of 119, this is 97 of those patients that had had 4 lines or therapy 4 more lines of prior therapy, an area of high end medical needs. And I do point out that in Table 5 of our label, there's a mention of 41% of patients having extra medullary disease and 75% we're alkylator refractory. So this is very unique to our label and this call out of EMD, we think is a special one and one as you know that's an important part of our development program going forward and will be an important part of our continued promotion of our product. So really excited about the fact that commercial drug will be available to patients within a couple of weeks, so over the weekend printing the labels, doing the final touches on the packaging and we'll get that into the distribution chain. Moving forward to Slide 9. So how does compactive stack up in the competitive landscape? And here we've tweaked these columns to those that you've seen previously to focus on this subset of 97 out of the 119 triple class refractory patients and you see that the patient the numbers from an efficacy and a safety perspective have held remarkably true. So first of all, with respect to the label, our label is exactly as we thought it would be, in the triple class refractory population with four lines. As a reminder selinexor is in the penta refractory category, requiring the failure of 2 drugs in the image and 2 drugs in the PI category. And belantamab is in a triple class exposed population. With respect to the EMD, we have twice as a higher percentage as the other products approved in PRC or triple class refractory disease with 41% having this extra medullary disease, so again, a difficult to treat population, we see that the overall response rate and clinical benefit rate for the Paco compare well to selinexor and to belantamab, we see a very strong medium duration of response the median progression free survival of these responders in particular compared to the Karyopharm, selinexor product. Overall survival looks strong. It's also important to think about and to recognize dose reduction and COPAXO standing out in particular against selinexor with 27% of these patients getting a dose reduction. Of note on the belantamab side, the 29% of dose reductions was off of their lower 2.5 milligram dose as we know in their larger trial and cohorts with higher dose, there were significantly more dose reductions that were required for the product. And again another place where our label and our product stands clear is on the non hematologic toxicity side. I mentioned that our AE profile is one of the cytopenias that oncologists, hematologists are used to treating. But on the non hematologic toxicity side, we are truly differentiated. When you look at selinexor and fatigue, nausea, vomiting, diarrhea, etcetera, that has really challenged patients to get multiple cycles of that drug. And then of course the unique toxicity profile that we see with belantamab particularly here on keratopathy and decreased visual. So also to mention on the COPAXO side is the convenience, the 30 minute infusion every 28 days that we know will be embraced by the community oncologists and hematologists in the United States. So in conclusion, COPAXO has all the makings of a foundational treatment in relapsed or refractory multiple myeloma based on the strong efficacy profile, better tolerability and a convenient administration profile. So moving forward to Slide 10, so what is our strategic approach as we begin to commercialize, COPAXONE in the United States and in future geographies, it's a 2 pronged approach. 1, we want to become the leading treatment or choice for the new classes of patients that are indicated in triple class refractory multiple myeloma. And secondarily, we want to expand the market for these new mechanisms of action. So no more recycling of failed drug classes. So you can see that in the market today on the bar chart, we see the domination of the old classes and recycling of these classes and a smaller market share for the drugs with the newer mechanisms of action, but in the future we see this shifting and of course, we look to our OCEAN trial and our head comparison with pomalidomide to be part of the force in helping us with this second strategy. Moving on to Slide 11. So from a promotion and patient support perspective here in the United States, we are ready to go, ready to here in the United States, we are ready to go, ready to launch, launch propaxo. So this will be through multi channel promotion and patient support programs that we're proud of, glad to say that propaxo.com is live on the Internet as is our patient support program. So on the left hand side of the slide, you get a little feel for the professional promotion that will take place and is taking place with healthcare professionals, highlighting this PDC innovation, the release of payload, the cytotoxic payload uniquely in myeloma cells and the benefit risk profile of our drug. On the right hand side, highlighting the peer to peer KOL involvement that is taking place at the bottom middle looking at digital marketing and virtual congresses that of course will be important in the COVID environment, but most importantly, centered at the top is the work that we're doing to support patients, ensuring that patients have access and appropriate support throughout their journey with COPAXONE, looking to make sure that they have access through benefits investigation, prior authorization, any help with any managed care denials or support, affordability, we don't want we want to leave no patient behind. So alternative funding program, co pay card, free drugs and adherence, so along the journey making sure we're providing everything we can to support the continued journey with COPAXO to make sure that patients can benefit from it in a maximal way. Next slide is Slide 12. So as we know, multiple myeloma is an incurable disease. We've seen here over the history as new drugs are added, survival improves. So clearly patients are in need of new treatment options and now COPAXONE is available to help in this journey. So out of the gate we'll be competing in this so called spaghetti plot down near the bottom where we see products like Glenrep and Fovio competing, but our aspiration and ambition is much higher. And I point your attention to the middle of the chart where we see the strongest growth coming from, 1st of all, daratumumab growing at 40% and pomalidomide growing at 20%, these link directly to of course our clinical development program first with the Lighthouse trial and the combination with daratumumab and the OCEAN trial with the head to head comparison to pomalidomide. So we're at a good starting point, we have a good profile and we know a bright future. Next slide please. So clearly COPAXONE has a significant potential. So looking at this slide on the bottom left hand side, again, same messaging as the prior slide, 1st year sales will compete in the category here of these agents that are approved newly approved in the triple class refractory stage, but I turn your attention to the right hand side of the slide. This is where we play tomorrow. Pomalidomide, dollars 3,000,000,000 drug growing at 22 percent. Daratumumab, dollars 4,200,000,000 drug growing at 40%, the opportunity to make melflupin or pacaxel a foundational treatment in relapsed refractory multiple myeloma will enable us to help more patients achieve and receive the benefits of our product. Next slide please. So as you know, we're developing and have this development program linked to spanned the patient population, so the Horizon approval provides its approval in triple class refractory patients who have received at least four lines of treatment. We know that that pool of patients overall independent of line, the triple class refractory population is at 20,000 and growing along with the EMD patient population and pool. As we move forward, our head to head trial versus pomalidomide may enable single agent use in 3rd and fourth line settings and that essentially doubles the population available for treatment with COPAXONE and looking even further out the Lighthouse trial and other combination trials, the combination with anti CD38 should enable second line use. And again, the population increases. But it's not only the number of patients that increase, but the duration of therapy that patients are able to takes, so moving from 3 to 4 months with in later lines to 10 to 14 months when we move to the second line. So again, a very significant commercial potential as we move forward. Moving ahead to Slide 15. So a really critical next milestone for us, the top line results for the OCEAN trial, a critical and key label expansion opportunity for us, these 4 95 patients, as you know, have been accrued. We're tracking the primary endpoint of PFS and events, this is an event driven trial and we're on track for top line results in Q2 of 2021 and likely a peer presentation of the data, we would expect sometime in the September timeframe. This is built on a strong foundation of evidence that we've seen in our early studies with our projected PFS, medium PFS of 5.7 months and looking at the MM003 trial that achieved helped to achieve the approval of pomalidomide with a 3.6 month median PFS, and we've largely seen these trends hold up for pomalidomide most recently at ASH in the APOLLO trial, so really feel good about this trial and the prospects for this trial. And again, our primary aim here is to stop the recycling of classes here of lenalidomide to pomalidomide. Next slide please. So there are 2 ways to win here as we've talked about this head to head study with pomalidomide and the chart on the bottom left speaks to that with point estimates of hazard ratio of 0.8 or less would be a superiority win, a clear and large win for COPAXO or Melflupin. In the non inferiority, a hazard ratio of less than 1 would prove non inferiority versus pomalidomide. Either of these outcomes would provide a significant commercial boost and we believe uptake for COPAXONE in the marketplace in earlier lines of therapy and positively impact our label. On the left hand on the right hand side, we see that in meeting the primary endpoint FDA and EMA no brainer with respect to confirmation of our accelerated approval and incorporation into the label, in the non inferiority case with EMA, again clear in terms of confirmation and inclusion in the label and with FDA per usual would be a data driven decision and of course we believe that a numerical win here would result in a regulatory win, but that remains to be seen. So really excited about Q2 and our top line results on the OCEAN trial. Next slide, please. We also have the Lighthouse study. This is based on positive anchor data that was presented at ASH, an overall objective response rate of 73% and an impressive median progression free survival of 12.9 months. So this trial will randomize 240 patients comparing melflupin dex plus daratumumab versus daratumumab alone. As you know, this trial has been initiated and we're currently accruing patients. So really excited about adding combination to our label in the future for COPAXONE. Next slide please. So looking at the news flow and major value drivers for us as a company, I'll point to Q1 2021. So pleased that we're able to commercially launch COPAXO in the United States. And looking ahead to Q2 of 2021, it's the top line results for OCEAN that will be another critical milestone in our journey to help more and more patients with relapsed and refractory multiple myeloma, application for conditional marketing approval for Europe it's something that's still on track, next drug in the clinic, the first patient in for OPD5 in the COAST trial. And as you see moving forward, we'll have results on various clinical trials that actually will positively impact our label, the BRIDGE study, the PORTGE study, last patient in on some other key trials, and importantly, the program will continue. 1st patient in on Lanturn, our trial in extramedullary disease will kick off in the second half of twenty twenty one and we'll continue to work on the lifecycle of melflupin or propaxo with signal seeking trials in other indications. So very excited about the future as well. Turning to the last slide. So in summary, COPAXONE is now available in the U. S. To address a growing unmet medical need. We will continue to bring hope through our science at Oncopeptide. I want to thank you, our investors for your funding, our patients for their trust and our employees who operate passionately, courageously and collaboratively with a belief in the science. So thank you and we will move to the Q and A section. Thank you. Our first question is from Peter Welford from Jefferies. Please go ahead. Hi. Thanks so much for taking my question and congratulations on the approval. I guess, two questions. I'll stick And the first question, I mean, I think it has to be asked is can you please disclose for us the planned list price of the PAXO when it's launched in a few weeks' time? And then secondly, could you possibly just detail any other requirements that the FDA has for the approval? I guess, I'm thinking beyond, obviously, it could be the ocean or the lighthouse trial for conversion to a full approval. Are there any other post marketing requirements or things we should be aware of and are there any requirements with regards to physician education, I guess I'm thinking any REMS or anything like that we should be aware of with regards to onboarding patients and physicians for use of the drug? Thank you very much. Yes. Thanks, Peter. Great question. So I'll actually I'll hand I'll make a comment on the last part of the second question first. So no, there are no REMS here. This will be a very straightforward. We were very pleased at the early interaction with the FDA, no ODAC, the benefit risk profile and the toxicity profile very, very clear here. So no need for anything like that. With respect to the lift price, COPAXA will be $9,500 for the 20 milligram vial. That equates to at least about well 19,000 for a cycle of therapy and you should expect for your models from a forecasting perspective to realize about 80% of that after our growth to net reduction. I'll turn it over to Klas to talk about the post marketing requirements. Yes. Thank you, Marty. And as Mario already mentioned, we do not have specific programs there and we are actually pleased with the post marketing requirements and also in the requirements that have been set for us, there are some other requirements, but those will all be covered into our current clinical trial program. So we do not have to initiate specific studies to confirm the approval of Pipexo, when it comes to education physicians, we will, of course, do that with regards to the psychogonias, but there is no requirement as such from the FDA imposed on us. And our next question is from Victor Sundari from ABG Sundal Collier. Please go ahead. Hi, good morning. First of all, congratulations. I've been following the company for a long time. I know how hard you have worked to get there, so really happy for you guys. Yes, so my first question is also a bit there on pricing and your launch. So you have to get the math right, what would that price be per month? And is there anything left here in 2 weeks in terms of key recruitments to get you started? How many sales reps, for example, do you have right now? Thank you. Yes. Thank you, Victor. So in terms of the team being in place, they're there. We do not have openings. We have a full team, very motivated to get started. Once we receive the acceptance of the file for accelerated approval, we built the team, trained the team and quite honestly, they've been chomping at the bit ready to go. So they're in place and really, really excited about getting started. So sorry, I missed the first part. Could you just kind of repeat that part of the question? Yes, the price per month, is that the same as 90,000? Yes, yes, exactly. So it's so the list price would be 19,000 that assumes the 40 milligram utilization, which of course is our dose and but again in your models, there would be based on discounts into the trade and other mandatory discounts about 80% of that to get to the net price, so it'll be somewhere in the $14,500 to $16,000 range in terms of net to the company. Okay. And on your confirmatory study, Could both Lighthouse and Ocean be enough for getting a full approval? Or is there anything that FDA Sat there with regards to your confirmatory study, if OSHA would fail for example? Either of those studies could be the confirmatory trial, either of those Phase III trials Phase III studies. Okay. Perfect. And just a last question here on extramedular disease. What would be the way forward there for getting, say, a specific mention that you could use the Paxil for these patients? I know you start you said you would start a study here in 2021. Would that be enough for expanding the label into E and P? Or how should you think about that? Yes. So the good news is the current label and I'll tee up class 2 to talk about EMD in our program. But with the inclusion in Table 5, that is unique to COPAXONE, I think recognition of this large patient population, we will be able to speak to this as we promote the drug and certainly what we see with our product, when we look at the intent to treat population in the horizon, pretty unique and strong numbers and this holds true as we move to the triple class refractory segment of 119 ended this pool of patients that are in the label of 97. So there will be ways to kind of address the early signals here. Klop, do you want to talk about the EMD program? Yes, sure. And of course, we are actively looking at opportunities there to include EMD in the label a bit more. LANTURN is a combination trial with bortezomib and dexamethasone that we will start this year. We will run the trial as per regulatory requirements, so it's all set up to be used for regulatory interactions should we want to. And we will have further conversations with the FDA about AMD being part of our label in the future. So far, AMD is not seen as a separate disease entity. So it's not something that you could just add as an existing indication. What we do see is that even in the case it would not land in the indication section that if we have positive data confirming the signals in E and D from Horizon, this will be a significant signal to also the healthcare providers to have the PPX still to their to help their patients with extramedullary disease, we will very we feel very confident that Lantern will give us the requirements that we need. Yes. And just a quick final question for me. I thought that you mentioned something about not going high on a higher dose there, Referring to your dog study, how should you think about, for example, conditioning regimens before stem cell transplantations? Is that anything that could inhibit the use there? Or what is your thinking? Yes, very good question. And this basically speaks about the broadening of our program to OPD5. So with nopluthen, with its extreme efficacy that we see at the dose already at 40 milligram, we just don't have the data to, I would say, safely allow going higher in patients with RR. And then given the profile of the drug, we could see some people wanting to use it in the future, especially given the well tolerability of this drug. However, we haven't tested that. And for that reason and for other reasons, we have also brought an OPD5 into the clinic for which we filed the IND last year, where we will start the COAST trial, and that's a slightly different formulation when compared to melfluthen where we will be able to study the drug in higher dosages in the stem cell transplant setting for moflufen, we kept our use at 40 milligrams. Okay. Thank you very much and congratulations again. It's Jacob here. Could I just have a comment to the last question? So basically, you don't need to read anything negative into that, the comments from the FDA regarding ablation. The key point is exactly what Claus said. We haven't conducted a dose finding. And it's a warning shot to clinicians that you cannot think dosing as you would dose any other alkylator, and you need to do a proper clinical study to find the right ablative dose. It's not that it's not reducible for ablation, but outside of a clinical trial setting, don't think about this as a standard escalator because the efficacy and safety curves looks completely different due to the power of the drug. That's the message that makes. And basically, even to make it more clear, this is something that we asked ourselves for to get this into the label to make this very clear to the Prescriber. Exactly. Thank you. I'll keep that in mind. And our next question It's from Susana Van Voorheesen from Kempen. Please go ahead. Hi, team. Good morning. Nice to sum. Big congrats on the approval. I have a couple of questions. Maybe can you elaborate a little bit on the FDA's consideration to Look at the subset of patients that had 4 prior lines of treatment. They excluded patients that were primarily refractory. Why is that? Maybe you can shed some color. Yes, maybe I'll start and then I'll pass it over to both Klas and Jacob to make comments. I mean, I think the thing the key thing here is about unmet need, right, and accelerated approval and finding that space where no other drug is approved, your label is somewhat unique. So throughout the process that patient pool changed just a little bit, I think the final change was 5 patients who were intolerable to their prior therapy took us from 102 to 97, but maybe Klas and Jacob can provide some better detail here. Maybe I can start and then hand it to Jacob. As I know, Joe can help us understand thinking there with regards to the historical approval as well. I think when it comes to our data, we had the large majority of our efficacy data in 4th line plus patients or in patients who have had at least 4 prior lines of treatment, so the study basically couldn't support in terms of numbers of patients earlier lines of treatment from a pure data perspective. However, if you look to historical approvals, I think Jacob has some interesting thoughts to share there. Absolutely. Thanks, Charles. I think, Sannath, that this is a very tricky question because I take it from a different angle. The FDA really wanted to approve us. But on the other hand, you had 2 accelerated approvals behind us when we were at this time point. 1 of them had also been fully approved. And then at the regulatory agency, you kind of need to find like how do I define a patient population where you really have an unmet medical need, going back to mark this point, and it's a little bit of a negotiation actually to sort of find an angle where everyone can feel comfortable. It doesn't have too much to do with data, etcetera, it becomes a little bit like a barter. And this was just one of those pizzas to get that into place. And I actually take it more like they really wanted to approve us, but with the recent events with accelerated approvals, etcetera, in this space, they just needed to find a patient population where they could feel comfortable that they could motivate and accelerate their approval for a new drug, 1 more in multiple myeloma, and I see it as a strength. And then exactly, I don't think it has any major impact on the drug as such, it's just part of the regulatory discussions that you have when you hit the finishing line. Got it. Now that's very clear. Perhaps can you then share some thoughts on how it may work for patients that are heavily treated in earlier lines of therapy And become triple plus referred to already, for example, after the second line treatment. What are their options? And Also more in general terms to what extent is sterile label used across Midom and U. S? Yes. So maybe I'll start just with respect to the off label piece and then maybe have the others kind of talk about the patient pool. So clearly, we will be focused on promoting on label. Of course, there's some blurriness here with respect to lines of therapy and prior therapies that is going to be subject to the interpretation of healthcare professionals and managed care organizations in an area like multiple myeloma, relatively speaking with the payers, this is a pretty small category and not an area of high interest. But it will be important and we'll see back and forth between healthcare professionals and managed care organizations and payers examining and looking closely at times with prior treatments that patients have had. So we'll see and we'll continue to report on how that plays out from our perspective. I do note that the majority of patients, a high percentage of patients both with selinexor and blend rep out of the gate we're fell into this bucket and continue to fall in this bucket. And again, not seen as a real challenge from my perspective in terms of building COPAXONE into a very significant drug and a commercial success, obviously, each of these new and innovative therapies that are provided in this incurable disease where patients, I think on the BLENREP study maybe went up to 21 cycles of therapy, there is a need for new drugs to positively impact patients and to provide hope to move forward. So I hope that helps on the off label side. I'll have the others comment on potential benefit to patients in earlier lines of therapy. I think it's important to recognize that this is a very fast moving field as we all know with drugs being used upfront more frequently, new drugs entering the market. I'd like to touch 2 aspects there. And then Jacob, maybe you can weigh in afterwards. First is the fact that a lot of people don't really know what a line of treatment is. Although it seems to be clear in people's mind, it is important to note that a dose increase, for example, an unplanned dose increase already satisfies the requirement for a line of treatment as well as adding a new drug to an existing regimen, so you actually reach for or line more spore lines more lines of treatment pretty fast, which we will have to educate on as well. So that is first. I think the other piece how to look at is that you basically have the 3 main players, image, PIs and then the CD38. And then the anti BCMA will move into that bucket as well eventually, being it already with Landrep, but for sure with CAR T and the bikes. And then you have the kind of second bucket is where you actually recycle drugs and where you have some newcomers. And I think the newcomer then being selinexor, Pipexo, recycling of all drugs, we feel that we feel confident that we can play an important role in that second bucket and being the kind of winner there. So there are 2 aspects. 1 is the lines of treatment aspect can be read in various ways. And the second part is that we feel that we are the strongest amongst so to say, 2nd bucket there. Great. Okay. Got it. And maybe just one So, Nicolas, Jacob, you want to add something? I just wanted to add one thing. And what we're doing now is that we try to crystal ball together, right? And I think always one should look at the recent past when doing that and how it plays out. And as everyone said, the line definition is a bit blurry. Patients have more lines than what meets the eyes already. But and the second thing is, of course, the abundance of label use that we don't promote or anyone promote, but it's just a fact in this field, if you look historically, what is dominant for use is the refractory status or the pre requirement for pretreatment for each patient. And there we got triple clot refractory, which is exactly what we want and we're very happy about. The second driver it's ease of use and tolerability. And here, we have a drug without REMS program and a 30 minute once monthly infusion. So when we try to crystal ball, we obviously feel that we have a very good position here to take a good patient share and help many patients. But then we'll just see we have to see how this plays out, of course. Got it. All right. And then maybe just one question to double check-in The mention of E and D in the label, is that a unique thing for Perfaxo? Or is E and D also mentioned in the blender Label sessions. Yes, that is unique to our label. And again, you'll see that in Table 5 in the clinical sector. Okay. All right. Great. Thanks a lot. Thank you. Our next question is from Patrick Ling from DNB Markets. Please go ahead. Hi, good morning and congratulations To the approval, just a couple of short questions. Could you elaborate a little bit what is happening with the expanded access program? And also how many patients was actually included in that program? Will they start paying for the drug now immediately? Yes, so maybe I'll handle the U. S. Part of that and then yield to cloth because it's evolving picture in Europe and we've got good news there. So we've never really disclosed in terms of number of patients. We had quite a few centers open. It's provided a fantastic opportunity to share updated information with healthcare professionals across the United States, very pleased with the program, and those patients would be transferred to commercial drugs. That would happen over the course of a few months. We are a couple of weeks away from having a drug that will be fully into the channel as I kind of mentioned and ready for patients, so this could take a little bit of time depending upon where the patients on the program are in their course of therapy and Klas, if you want to touch on Europe and anything you want to add on the U. S, please feel free to do so. Yes. First of all, in the U. S, we have still patients enrolling until last week. So we cannot give a definitive number there as well, but I think it's good to mention that given the success that we saw in the U. S. And especially the interest in the program, we have decided to also have an Expanded Access Program for Europe. Currently, we are close to opening 2 cohorts countries, Germany and France, so we will have ipaxo available for patients there as well or better said naphthalene fluffenamide. And we are also actively looking into options for named patient access via early access program in the rest of Europe, so that is very much on the radar to open soon and that is clearly built off the interest that we saw in the U. S. For our ex Pondertexas program. Okay, great. Could I also ask you, When you talk about releasing top line data from Ocean in Q2, what Type of data are we talking about? Are we getting more or less full data set? Or will it just be sort of a mentioning that whether you reached superiority or not? And then the full data set will come at the Scientific Conference in September. Yes. I'm happy to comment on that. As you may appreciate, this is a big Phase III trial. And once we get the data in, the data comes in various batches. And we want to be able, want to have a big presence at the scientific meeting in the future and therefore you cannot disclose too much because then you are not bringing the news at a conference. So what you can expect with top line results is basically whether the study has met its primary endpoint, yes or no, and that being either a non inferiority or a superiority result. For any further details that will be disclosed at a future medical conference. Okay. And you mentioned the medical conference in September, which one would that be? We're still actively discussing that internally, so I cannot comment on that yet. Okay, great. Thank you. That's all for me. And again, congratulations on the approval. Thank you, Patrick. That's right. And there are currently no further questions. I will hand the word back to the speakers. Thank you. Thank you very much, operator. And I want to thank everyone for participating. I feel very fortunate, very lucky to have joined this company some 7, 8 months ago and just jumped on the back of folks like Jacob and others in the company and it's been a great 8 months so far and I have a lot of pride for what we've accomplished with this approval, but I really want to give the final word and farewell to Jacob just reflecting on his contributions, his vision, again, his perseverance, please take us to the conclusion of this call, Jacob. Thank you. Thank you so much, Martin. I just want to thank you as shareholders for having supported us through this period. We went to the Stock Exchange in February of 2017 with a promise of taking this drug to approval. And today we have fulfilled this promise that it wouldn't have been possible without your support in terms of finances and your support through all the ups and downs through this year, now a new chapter begins and our next promise is to make this wildly available for patients, first in the U. S. And later in other geographies. And I hope that you will continue to show trust in us since we have actually delivered on our promises so far. On a very personal note, it makes me immensely proud today. And to hear Marty present the company so well feels great. So thank you very much, everyone, and thanks for all your support over these years, and we hope to continue to show that we can deliver on your trust in us as a company and as a management team. Thank you.