Earnings Call: Q1 2020

May 26, 2020

Hello, and welcome to the Oncopeptides q one report 02/2020. Throughout the call, all participants will be in a listen only mode. Afterwards, there will be a question and answer session. Today, I'm pleased to present CEO, Jacob Lindbergh. Please go ahead with your meeting. Thank you very much, and a warm welcome to everyone. We're gonna go through an update across our studies and what has happened during the quarter a little bit, and then, of course, also end with the financials. At the end, we will also allow for questions and answers. So please wait until then, and we'll answer to the best of our ability. So this quarter is all about setting the stage for our submission and for commercialization of no solution. And that will very much be the backdrop of today's discussion. Please go to Slide number three. So looking at recent highlights for us, this quarter has, of course, been very much, in the shadow of the COVID nineteen pandemic, where, as we have stated before, we have been on the fortunate end of things. Both our pivotal trials have been affected to a minimum compared to a lot of, other companies, and with that, I mean Horizon and Ocean. Ocean that was fully recruited just recently. We will come back to that. But all the signal seeking trials, have been on pause. We believe that they will be on pause basically right now. That is in line with what we see other companies doing, and we have had several interactions with the hospitals, the providers, as well as key opinion leaders and the regulators to discuss what it's proven to do. And, we believe that we are more or less back to normal in terms of clinical study and clinical study conduct in light of the pandemic right now. So we should be able to do that. This this, of course, also means that we can, continue to try to initiate our new trials that we had planned. Please note that when you pause the initiation, you don't just stop the clock. You need to redo certain elements of your preparations, so we will come back in terms of the timelines for when the planned studies can be initiated at this at a later date. We got the study results from o 12 m one, our old phase two study in Lancet Hematology. That was also a big milestone for us. It's it's a great journal with a high so called impact factor. And we also got the editorial in that, journal, and we're gonna come back to that today, which is literally what you wish for when you get your data published because that is the article with the most impact that is then selected by the journal for comment by an independent KOL. We also presented the top line results from Horizon, our study that originally wasn't planned to be a pivotal study, but ended as a pivotal study given that the main bulk of the patients in that study belong to what is called a medical need population from a regulatory point of view and that our results were so strong in that population. So we are now then heading towards the NDA submission, which is the next bullet on this slide. We are on schedule for an end of Q2 submission to the FDA, And that what we're looking for is to see we seek market authorization to use Melsusen plus dexamethasone for the treatment of myeloma patients with triple class refractory disease. Please note that this is what we wish for. We'll see what the regulator tells us in response to our wish. But of course, we have had ample of regulatory interactions over the last year. So this is what we expect, but we have to see. The submission timeline for that is then eight months in total from the time point of submission until according to regulations. This submission should result in market authorization unless there's a problem with the submission, and the historical average is around five and a half to six months. So that is why the guide that assuming no major problems with this submission, we should have a market authorization at year around year end. That is six months after the submission has been sent in. But this could also be early twenty twenty one, or it could be slightly earlier, as well. So we just have to wait and see. The phase three study, Ocean, is fully recruited, four fifty patients. We reported that just a few days ago. If you go back in time when COVID nineteen, the pandemic hit, we realized that recruitment went down initially, and we gave guidance for that this study would be fully recruited April. It ended up roughly three weeks later. The key factor that we haven't calculated at that time was that Eastern Europe was fairly unaffected when we went out on the on the COVID nineteen update webcast. And in the end, Eastern Central Europe actually has behaved at the hospitals more like Southern Europe and not like Northern Europe, and we haven't estimated that. So that slowed things down a bit further, even though they are quite back on track right now again, but now the study is fully recruited. Another item that we went out with this quarter was that the Horizon dataset not only validated the activity of Melslufen in myeloma, it was also validation of our peptide drug conjugate platform, the PTC platform. And we also unveiled the two drug candidates that we have in the pipeline in the preclinical setting, and we gave guidance for when these might be ready for the clinic, and we'll come back to that. And then we have a bonanza of preclinical and clinical abstracts to be presented at various conferences here, which actually marks the highest frequency of scientific publications and communications in the company's history. And that includes then it was controversies in multiple myeloma now recently, then we have ASCO, we have EHA, and we have AACR coming up. So it's it's a it's a very rich communication environment from us right now from a scientific point of view. And finally, we raised SEK 1,400,000,000.0 in the direct share issue in May, before costs. And this marks actually one of the biggest, if not the biggest, direct share issue in the life science sectors in Scandinavia. So it's also a apart from being a major milestone task, it also will enable us to fully launch this drug and take us far into the future in terms of and we'll come back to more exact guidance, and Anders will do that, but this has secured the launch phase at least of Melsusen in The US in terms of finance. Next slide, please, slide number four. So this is a familiar picture of our clinical study program. I won't go through all the arrows. But as you can see here, we have added two arrows at the bottom, and that is the AL amyloidosis trial that was paused due to COVID nineteen and is about to be unpaused. And then, of course, Lighthouse, which is our second phase three trial that should have been initiated around now. But due to COVID nineteen, we pushed out the initiation. And we'll come back to guidance, but it is unlikely that even if we, on pause, and can do this, that this will be able to be initiated before the summer. It it will most likely be straight after the summer, but we'll come back with more exact guidance. So what market segments and patient populations, do our trials actually, address? Please go to slide number five. So here you see basically the patient populations in myeloma, in the boxes and then the trials that address these patient populations. The first, we have the Horizon trial that where we hope and wish to get a label in triple class refractory patients. We also have really good results in patients with extramedullary disease and patients with high risk cytogenetics, To what extent we can get this as part of the label with the FDA, we don't know. We are hopeful, but we don't know. But this is all both these groups or all three groups are groups with a significant unmet medical need where our data is the signal is very strong that we're doing different making a difference here. So we'll see exactly what the label contains, but it should at the minimum contain triple cross refractor patients. Then we have two boxes below here, which is the label expansions or the initial market authorizations outside of The US that we're going for. And basically, these are patients that are relapsedrefractory, so they don't need to be triple class refractory. They could be single class or double class refractory patients. So they have started to progress rapidly while on treatment, but they haven't tested all available, and approved drugs yet. Ocean addresses roughly half of these patients, a bit more than that, that only received one drug plus steroid. That's the first blue box. And then Anchor and Lighthouse, of course, addresses patients that received two drugs plus steroid. This is very much boils down to local, how you treat patients locally, what what the treatment algorithm is, but also the health status of the patient. If you are a younger, healthier patient, you more are much more likely to get the combination. That is two drugs plus steroids. If you are an elderly frail patient, I. E, the majority of myeloma patients, the likelihood is that you will be treated with one drug, plus minus steroids. To understand a little bit better how this can correspond to market potential looking at U. S. Numbers, please go to slide number six. So on slide number six, we have prescription data on various drugs in myeloma for The US until December 19, so December. And and I want you just to focus on that December 19 time stamp. That is the far right of this graph, and look at those lines. Because even though this is a simplistic overview I'm gonna give you right now, it gives a very good guidance for how patients actually are treated. It it's the treatment algorithm comes through in these numbers. The first thing you see is that the two top lines are Revlimid and Velcade. These are the two biggest drugs in myeloma still to this day. One is an Imid, the other one is a proteasome inhibitor, and these two drugs are what you get as a patient when you are diagnosed with the disease. Either you get them one at a time sequentially or you get them in combination. And that is why if you look at the patient numbers to the left of the on the y axis, you see that it's around fifty to sixty thousand patients per year in The US receiving these drugs. Once these drugs fail you as a patient, I. E. That the disease become resistant to them, you come to the next tier of drugs, which are the two blue lines in the middle. One is Darzalex or daratumumab. One is Pomalyst or pomalidomide. These two drugs are once again used either together or in sequence, sometimes together with something else, but these two are the mainstays of a patient that has started to progress while on therapy, and in this case, on Revlimid and or Velcro. Now once these two drugs, that is DARZALEX and Pomalyst, fails you as a patient, you come to the bottom of this chart. And and and I have said in multiple meetings, I call this the spaghetti or the confetti because it's a mixture of lines around 10,000 patients per year, and you see multiple drugs here. These are the drugs that are then part of the fundamental retreatment schedule because the first four lines represent all the three major classes of drugs, proteasome inhibitors, IMiD, and anti CD thirty eight therapy. So the spaghetti, the confetti is the retreatment bucket, where, of course, you try to change the individual drug in each class, but with very poor outcome in general. Now if you were to look at our studies, you can actually see why we have designed our study program the way we have, because Horizon addresses the spaghetti or the confetti at the bottom. And, hence, if you're successful with Horizon, you get approval, and you can position your drug in a good way in the treatment landscape, you should get between, you know, five to 12,000 patients, something like that, on treatment on an annual basis from that study in The US. Then we go to what we are trying to achieve in ocean and lighthouse. In ocean, we go head to head with pomalidomide. That is one of the blue lines in the middle. So we're trying to compare ourselves in a slightly earlier patient population, significantly larger, longer treated, and that is then what ocean is trying to do to establish a foothold that also earlier patients should receive nosulfone. And here you also see the reason for Lighthouse, where we combine ourselves with daratumumab. Once again, it is one of the two blue lines in the middle. So while we are not, with this program, addressing the newly diagnosed patients, I. E, the Revlimid and Velcade lines, our two Phase III trials are trying to establish a position in earlier relapsedrefractory patients, represented by the two blue lines in this chart and horizon, of course, at the bottom, the spaghetti of the conceptus. So here you see also the logic behind the design of the program and why we have laid out the studies the way we have. So how does these studies turn into patient numbers? Slide number seven. Thank you. Here you see The US patient numbers represented that we think are addressable with the various, studies that we have. And you can see here that the horizon represents is represented here by the two orange bubbles, both the triple plus refractory patient population as well as the extramedullary disease and high risk patient populations. Please note once again, we don't know exactly what we're gonna get in the label with regard to EMD and high risk, assuming we get approval. Ocean addresses then a slightly earlier patient population with single and double class refractory patients, represented in blue, roughly twenty five thousand patients per year in The U. S. In that pool, and then the combination studies in Anchor and Lighthouse addresses the green area, which is then roughly 20,000 patients that receive combination agents. Like I said, the majority of patients receive one drug type steroid, the blue, but it is fairly close, almost fifty fifty. Now what this picture doesn't contain is the fact that treatment durations vary wildly between these areas. So in the orange field, the median treatment duration, the average treatment duration, sorry, is around four to five months for a patient because so many patients progress very rapidly. So you have patients that stay on the drug for a year or so. You also have a significant number of patients that progress very rapidly, unfortunately, so four to five months. Once you go to the blue area, you are more around an average of maybe around six months, and then you start to get closer to here in the green. So that means, of course, that the value from a pure capitalistic point of view is higher, the further to the right of this this in this figure that you get. The green patients are much more valuable, given the duration of treatment since you get paid on a monthly basis than, the other areas here. So in terms of market potential, let's go to slide number eight. Thank you. This is here, you can see that actually relapsedrefractory patients, when we started this journey, it was actually the smaller market compared to newly diagnosed. Newly diagnosed here is the difference between relapsedrefractory and all so it's a roughly $6,000,000,000 market. And when initiated this journey, actually, that was the major part of the market, but the relapsed refractory segment is the fast growing segment, and that this $13,000,000,000 with The US and rest of the world is, of course, the addressable market for us in terms of our studies. That is the market that we are in best and hope to get a good share in. Okay. Let's go to slide number nine. I mentioned this that both of M1 got published in Lancet Hematology, and we also got the editorial. And I recommend everyone to read the editorial, because it really touches the key point of our entire program, does a modern alkylator have a role in the treatment of multiple myeloma? And we were extremely happy to see this editorial being published. And this editorial was then connected to our old study of M1, but as I stated, during the quarter, we also reported top line results from our Horizon trial. Slide number 10. Thank you. So our top line data from an investigator assessment point of view was twenty nine percent response rate for the overall population and 26% for triple class refractory. What I can highlight here is actually the independent review committee data. That is what the regulator care about. And the fact that that data actually slightly improved is is due to the quality of our internal work and the assessments we have done. It's highly unusual. The independent review committee data is always worse than the the the data from the company, but it it will help us in the regulatory process. And the key question is, of course, how does this compare? Because we are not alone in trying to address this unmet medical need, and therefore, go to slide number 11. On slide number 11, we benchmark our data from the Horizon trial, and please note that in this slide, since we haven't released the full dataset yet, this is actually the data we presented at ASH, an interim data point. But we see milsulphin to the far left. You see selinexor from Karyopharm in the middle, and you see belantamab, which is lactose mixed lines antibody drug conjugate targeting BCMA to the right. The good thing is that these are very comparable patient populations. And while there are a lot of numbers here, I just would like you to focus on three lines in total. The first one is the overall response clinical benefit rate. And if you look at these numbers, I just read them out loud first, 26, 37, twenty five, thirty nine, 31, 34, They are the same. These three drugs are the same. The amount of tumor burden reduction you receive with these drugs are identical. So there, they are not different, even though they represent different treatment classes and modalities. Duration of response, however, or in other words, for how long is a patient disease free while on treatment if they respond to it. And here you see that selinexor is at a clear drawback compared to belantamab and melsufen. So at this point in the analysis, selinexor has a minus compared to belantamab melsufen. But then if you look at the toxicities where melsufen, of course, have hematologic toxicities, but seventy percent of patients can maintain dose, so it's not a big problem. The non hematologic toxicity profile of these drugs are very different. And I won't go into details, but as you can see, nosuphem's list is very short when you create data in the way that the FDA is doing as a standard in in in their label text and analysis. While selinexor has a pretty significant list, unfortunately, of metabolic and gastrointestinal side effects, emblematic has its ocular toxicity blurred vision with, some blind patients. So all in all, we think we actually have then the best risk benefit profile of these three drugs. Obviously, what we think is not the important thing, we need to understand what the regulator thinks. But we this is why we are sending in the submission, because out of these three drugs tested in the same patient populations, we feel that we have efficacy in line with the lump sum up, but with a better safety profile. And selinexor has actually a worse safety profile and worse efficacy profile in our opinion. Please note. Slide 12. Thank you. So the submission based on this dataset is on track for late q two release. We are launching an early access program in The US for triple trans refractory myeloma patients. We are right now in the middle of those works, and it should we should be able to have a first patient in later in the summer. Mhmm. And we are also, of course, in in in line with sending in the submission, we are building up the US commercialization organization in The US, where we had 30 full time equivalents by the March, and that is growing rapidly. We are actually on on schedule to deliver the plan and the organization there, and Joseph Horwath is doing a great job as our head of the president of North America. So that was regarding the submission in Verizon. Let's spend just a little bit of time on Ocean on slide number 13. So as you know, it was now fully recruited, and it's a head to head comparison with pomalidomide, I. E, we are addressing the middle segment of the market chart that we discussed before with this trial. It's a trial where we the null hypothesis, as we call this, that we are superior to pomalidomide, but we can also meet the endpoint if we are non inferior to pomalidomide. So we have two different results that both would mean that the study was a successful study. Of course, we hope and believe that superiority is the result. Right now, what happens now? Right now, we are waiting to receive the right number of events from this trial. We need a certain number of events to do the statistical analysis, and we don't control when those events happen because an event is that the patient relapses in his or her disease, that is that the tumor is growing again, And we just need to get the data from the various hospitals. And as a paradox, the longer it takes for that to happen, the better it is because that means that something is going on in the study that is positive. We, of course, don't know which arm, but since we basically know how comalidomide performs, any any delay in getting the events should mean a good probability that this is due to our drug, but we don't know that until we have looked at the results, of course. So we are following this very closely right now, and we have given guidance that originally this was due to end of Q3. And as you know, we said when the COVID-nineteen hit that the slight delay in finishing the trial should also translate to that time point. So now we are just saying second half of this year in the news flow. The key assumption for this trial is that pomalidomide and the sister molecule lenalidomide, that they have cross resistance. Please go to Slide number 14. There has actually been some discussions regarding this, and I would argue that right now, everyone is in agreement that there is a significant degree of cross resistance between these two drugs, and that is what makes this head to head trial actually trial with a good chance of success, rather than a low probability of success. And on this slide, you see that the multiple of data sets showing that pomalidomide loses between 2550% of its activity. There are two other studies showing exactly the same thing. One is a study by David Siegel that was recently published in British Journal of Hematology, and the last data set is the OPTIMISM trial from Celgene. Celgene has tried to position both of the later two trials as trials where this it shows that pomalidomide works even though the data suggests the complete opposite. So we're very happy that they talked about this, but there are three big data sets saying the same thing. All roads lead to Rome, twenty five to sixty percent reduction in pomalidomide activity in recently say lanolidomide failed patients. Early on, I talked about our platform, and I just want to briefly go through that, slide number 15. The platform is we call it the peptide drug conjugate platform. We put a very small d peptide to a toxic payload that has two specific enzymatic motifs that actually results in an increase in antitumor activity. There are a lot of there are a lot of things around these motives that we don't fully understand still to this day, as is the truth with many other drugs as well out there. What we can say is it doesn't just deliver a payload, it actually changes the molecular fingerprint of how the drug works. We don't utilize, for example, as an alkylator now with Loflufen, we don't even utilize the same apoptotic pathways with other alkylators. So we fundamentally behave as a mobile class. Looking at the activity footprint from this platform on slide 16 so slide 16, thank you. You can see that across a broad range of tumors, this platform has activity. There are some where the activity is lower, such as renal and colorectal cancer that you see to the far right on this chart, but otherwise, these enzymatic motifs seem to be key for the majority of cancers out there, which means, of course, that the indication broadening from this platform outside of myeloma is one of the key strategic tasks we have in 2021 and beyond. Where are there must be more patients than in myeloma that would benefit from a drug such as nosufen for one of the follow on compounds. And looking at the follow on compounds on Slide number 17. Of course, nosufen is the one that is furthest ahead with the submission now, but we also have two compounds that we have revealed, and that is OPD5 and OPS2. OPD5 is a compound where we have designed it to be utilized in conjunction with a stem cell transplant, that is a bone marrow transplant, in primarily hematologic malignancies. And then OPS two is a peptide drug conjugate with a slightly different profile than nalturfen. And of course, we will look carefully at the data for OPS2, we will come back to exactly which indications we will go with that one into. But in general, OPD5 will be ready for clinical use in 2021 and OPS two late twenty twenty one. So when I'm saying OPD five ready for the clinic in 2020 in this chart, that means they have all the data, but then you actually need to create the documentation for the regulator, etcetera. So realistically, clinical trials can start with OPT5 until early twenty twenty one. So going into the financing, and I think, Anders, you should take this part from slide number 18 onwards. Thank you. Yes. We're very happy that we were able to execute a very successful director share issue that we announced on May 5. We saw very high interest, and it was a little bit nervous process since the market have been been wobbly over time. So we were very happy that we were able to generate such high interest. The issue was roughly four times oversubscribed. So we were able to upsize it to the maximum size, rating roughly 144,000,000 or SEK 1,400,000,000.0. We were particularly happy to see that for the first time, we really saw wide range of U. S. Specialist investors coming in, and we mentioned in the press release that we received Dirtland, Farallon, Artisan and Oktogon as new shareholders. We're very happy to welcome them. But of course, we're also very happy that we continue to get a very strong support from our existing shareholder base. Without them, we wouldn't be here today. So a big thank you to all of the shareholders, and thank you for your confidence in that. Let's then turn to slide number 19 for the financial results. As you can see, the operating loss increased from roughly 134,000,000 Swedish to 297 Swedish. And on the left hand side, you see the graph showing why it's increasing. And, basically, the r and d costs are increasing significantly, going from 107,000,000 to 214. The lion's share of that is explained by increasing clinical costs. We have clinical and drug supply increasing to 158,000,000 in the first quarter from 73 last year. For example, the cost for the OCEAN study went up from 37.6 to 77.7. And you should should know that that a big part of that is large purchase of Pomalyst, but roughly 32,000,000 in the quarter. So the cost for for the OSHAIN trials are quite lumpy since we buy Pomalyst from time to time, and then the cost go up for that quarter. It doesn't mean that it will always remain on that level. We also saw a big increase in the Horizon study going from 11 to 26,000,000. It has become a pivotal trial. That was not what it was designed for from the beginning, so so the costs have gone up quite significantly. For the first time, we also include costs for the Lighthouse study. We have selected the CRO and have started to prepare the study, so so we will continue to incur significant cost for that study. The cost for the ANCHOR study has actually gone down, mainly explained that we did purchase a lot of drugs in the first quarter last year, but not this year. You also see from the graph on the left hand side that the the marketing and sales costs have gone up from 17.9 to 51,000,000. This is, of course, explained by the buildup of the commercial organization in The US. The full cost for the US subsidiary was 44,000,000 in this quarter, going up from 8.5 last year. However, not all of those costs are recorded in in sales and marketing. So we have roughly 14,000,000 included in G and A of the cost per user subsidiary, and that explains the increase in cost for G and A. Cash flow was SEK $313,000,000 negative, which is in line with the operating loss. We also have some changes in working capital that explain the difference between cash flow and the operating loss. And then at the end of the quarter, the cash position was SEK 617,800,000.0. That then does not include the financing. The pro form a number, if the financing would have been performed before March 31, then we would have had SEK 1,950,000,000.00 in cash. And with that cash amount, we have runway through q two twenty twenty one. So we're now financed to perform a launch and and all the clinical programs that we want to perform during that period as well. So so we're very well financed right now. You should also maybe note that the settlement of the financing will be carried out in two steps. We issued 6,100,000.0 shares already in May, but the second part of the share issue will be executed in July. So the number of shares will will increase by 6,200,000.0 shares in July as well. That was all on the finance side, and I'll leave the word back to to Jacob. Go to slide number 20. Thank you. So just with regard to news flow. On this slide, you see the news flow divided in two buckets. The upper bucket is the news flow that is added, and I'll come to that. The lower bucket is the news flow as it looked before COVID-nineteen, and then we paused the signal seeking trials. As I stated earlier, we now believe that we will unpause them within a very short time period, meaning that we will come back with updated news flow timelines for for for these studies at a later date. Right now, before we have unpaused it and have our full arms around the situation in regards to the type of patient recruitment, etcetera, we will see. We don't want to give any guidance, but obviously, the five boxes on the lower half of this slide will move to the right by and the question is, is it one quarter or two quarters? And we don't know that yet. Looking at the upper half, we have the last patient in the notion. We delivered that. The NDA submission remains, but we remain on target for a late Q2 submission to the FDA. And we now have top line results. We have put that, as you know, in the report we wrote second half of this year. The original guidance was late summer, August, September time frame, but that was before COVID nineteen. And, you know, we finalized the study roughly seven weeks later than March, meaning that something like that is reasonable to assume at least that it's added, meaning that we bumped this into q four, early q four. The main risk here, though, is that we don't control the events. And as I said, if the events take longer time, it's actually positive for us, but we just have to wait and see. We don't control that. So there's still uncertainty exactly when we will have top line results. We, of course, have the potential accelerated approval in The US. As we've said, the historical average is five to six months, which would put it at the end of the year. But there is a process ongoing with regulator from time of submission up to eight months, which would put that also potentially in Q1 in 2021. And then the potential launches, of course, at the same time as the potential accelerated approval. They are very closely aligned in time, just basically a day or so in between. Thank you very much. I leave the floor open to potential questions from me or Anders to me or Anders. Thank you. Our first question comes from the line of Christopher Yudi from SEB. Please go ahead. Hi, Jacob. And Anders, congratulations on the enrollment. Obviously, big news. So my first question, just on the timing of filing, know, so Karyopharm, they've submitted their sNDA. Obviously, selinexor is not standard of care, so there's no question of that being an issue right in terms of getting a conditional approval. That's the first question. Then, you mentioned, the slides on one of the slides here, you know, Hanker getting you being part of how you get to combo use on label. Do you expect ANCHOR to be sufficient to get dara and bortezomib combinatorial use on on the label? And, yeah, I think I'll I'll just start there. So thank you, Christopher. So, basically, selinexor is not part of standard of care. So for the submission and filing, this is not an issue. This would potentially become an issue if we if the submission was significantly delayed from us because then they could get their full approval and all that before we had time to submit. And that could actually change the landscape. But now we are on target, and they will not have any type of approval two to three weeks from now, four weeks from now. So right now, it is it is not good. As to your second question, no, ANKR will not result in any label language at all. And I and I know that, you know, regulators hate to to to hear this, but, you know, roughly half the combinations in myeloma are so called medical use combinations. That is combinations not formally approved, and that is based on phase two data. So ANCHOR, of course, can result in some We don't have the right to promote or push it, obviously. But especially in later lines, there's a lot of pick and mix going on, and then phase two data actually matters in that. And for that, Anchor can do something. But, obviously, with Lighthouse, we are seeking the formal label expansion into a combination. Yeah. Great. Yeah. That's fair enough. Yeah. Then then just on so r and d costs Well, so so ANCHOR and BRIDGE, I guess you you've you've said that the cost for ANCHOR went down, but there are cited as factors behind the higher R and D costs. Obviously, they've been on pause since, I guess, March. Right? So what's the current status in terms of n? And when do you think you might I mean, what what are the factors, let's say, that that might that would trigger you to press play? Yeah. What do you mean on on unforcing the study? I mean so we we have had both ad boards and KOL interactions and interactions with local authorities regarding this. And our opinion is that actually in cancer right now, it all boils down to safety. Right? Like, you don't want to impose safety issues on patients. What all the KOLs, all the local regulators say now, and I I'm I'm sure you have seen similar articles in in in in in Sweden and other countries as well, is that the biggest safety issue right now is that cancer patients are not getting the care they need for their disease, I. E, undertreated cancer is a bigger health risk for these patients than the COVID nine exposure, meaning that right now, all these institutions are pushing hard to restart and make sure that patients come to the hospitals, that patients come to receive their treatments, and that patients with potential cancers seek help to see if they have a cancer. And this is actually a bigger problem than COVID nineteen for this patient group right now. And and, of course, in that context, it means that we have an ethical obligation to to unpause our trials because the problem is the opposite from where it was two months ago. Yeah. So so I guess, like, the the the and the the consensus on COVID, I mean, to the extent that there is one, would be basically that one should probably expect a second wave starting in autumn. Does that you know, how how if the second wave comes, how would that affect things, which I mean, I guess you'd pause recruitment again. But is that is is are considerations about that a factor that goes into whether or not you're thinking about restarting or, yeah, re repressing yeah. Unplugged. Actually, right now, I would argue now when it's so much easier once you start to have we know roughly the data from the first wave. Right? And we can see is that, actually, that several patients group not receiving adequate treatment is as a big problem as COVID nineteen, and this goes for cancer patients and cardiovascular patients in particular. And I think that when the second wave comes, these patient groups with severe illnesses will actually be prioritized, and they will really fight to maintain treatment algorithms, hospital visits, etcetera. Of course, you don't want to do hospital visits unnecessarily, but to maintain treatment and and maintain diagnostics on these patients will be key to actually get a good epidemiological outcome from the whole COVID-nineteen situation. So the short answer is I don't believe a second wave will force our trials, actually. Okay. Great. And just last one before I get back in the queue. For Anders here, how should we think about, r and d costs over the remainder of the year? I mean, should we expect the highest in q four to become, you know, due to ocean? In q four? No. I think you should, expect them to be fairly stable during the year. Okay, great. Thanks very much. I'll get back in the queue then. Thank you. And the next question comes from the line of Patrick Link from DNB Markets. Please go ahead. Yes, hi. Good morning. Just a follow-up question to to Chris Stofer's question here before. When it comes to selinexor and their SA NDA, the answer today that you gave, Jacob, it sounded a little bit like you just have to file before they get an approval. Previously, you've said that you actually need to have your approval before they have their approval. Maybe you can just clarify what what the rules are really to to to be sure that your drug gets approved. Yeah. Absolutely. So, technically, the answer I gave before is the correct one, which is exactly what you reiterated now. We need our approval before they get our approval. But in practice, the submission and filing becomes key because the FDA has an obligation to maximize choice for patients, and it means that if they sit with two files on their table at the same time, they will determine and and they determine that nosupin is a drug that should get accelerated approval based on their data. They actually will and will have to basically prove that first and then take selinexor straight afterwards, even if it's just a day in between. So that means that actually the submission date becomes kind of important to make sure that they sit on all the data and can make their assessment before they come to a time point where they need to approve selinexor, so, in in in the according to the BOSTON trial. So, from a practical point of view, actually, the submission becomes kind of important here in terms of time. But from a regulatory point of view, it's absolutely the approval that determines everything. Okay. Great. And thank you for the clarification. Then then, also on the second follow-up when it comes to the Ocean trial and Lighthouse. I mean, now when Ocean is fully recruited and, I mean, the pickup in in, cost that we saw was due to to buying a lot of Pomalyst. Maybe you can elaborate a little bit how how these costs will play out, going forward, and will you have to buy more Pomalyst at some point? And then when it comes to the Lighthouse trial, I mean, now you started to initiate that trial. I mean, what should we expect overall for the cost for that trial given that, in this case, you don't have to buy the daratumumab drug, and if we compare Lighthouse to to to the OCEAN trial. 100? Yeah. So Lighthouse will be a much cheaper trial. It's much smaller. I I think the what's the latest patient number? It's one seventy or something. Yeah. Yeah. Just short of 200 patients. Yes. So so it's much smaller, and we will not have to to to buy the comparator drug. So so it will will, of course, incur cost, and that will ramp up during the year, but it will not be sort of at full pace until we have a lot of patients included. So the highest cost for that trial would probably be during 2021 and not in 2020. And at the same time, the ocean cost will continue, but they will start to go down, especially from from the first quarter since we have the big chunk of of formalities that we have to buy. So so more I think those two combined will be roughly stable over the next year or so. Does that make sense? Yeah. Okay. Great. Thank you. Thank you. And the next question comes from the line of Peter Welford from Jefferies. Please go ahead. Hi, thanks. Just two quick questions, please. Firstly, just with regards to The U. S. Commercial infrastructure, you said you've got 30 FTEs by the March with a ramp up planned over the future quarters. I wonder if you could give us some sort of, I guess, plan as to what sort of FTEs you should be thinking about over the coming quarters? And then by the end of the year, should we anticipate the commercial infrastructure in The U. To be more or less fully in place in the first phase? Or is any of the hiring and plans being held back until the approval is actually given by FDA? And then secondly, just on to the Horizon final data set, you will there also be an update on the duration of response? Or should we anticipate that more or less unchanged from the prior presentations? Sorry, what was I didn't get the last question, Peter. Can you Sorry, the duration of response. I appreciate your final You've updated the overall response rate and given us the AIRC data on that. Whether that regards to duration of response, should we assume that's more or less unchanged, or will there an update on the DOR as well for those analyses? Thank you. Yeah. Okay. Thank you. So in terms of the ramp up of the commercial infrastructure, you know, we we will right now, we're actually doing some analysis for the final numbers in q four, and that is has mainly to do with COVID nineteen because you're not allowed to visit hospitals in the same way as before, which means that a lot of the interactions between a sales rep and a clinician is actually done in the virtual environment now. So that might have implications for the exact FDA mix we want at the time of launch. But to give you a rough number, we will be around 100 people in Q4 just before the launch and then in The U. S. And then exactly where that will end up as the final number, we'll have to come back to that and give guidance. But the current plan is actually to be, for example, 81 at the end of Q3 and then with a continued ramp up in Q4, in line just before the launch. When it comes to the DOR, it will be updated as well. So we will update all the time to event parameters. What I can tell you is that we feel very comfortable with the time period that the patient actually from the initiation of Melsusan treatment until the patient progresses in that data set. We feel very good. We have a slightly longer time to response than other drugs, But if you look at the actual, the t three period that these patients have, it looks really, really good. That's great. Thank We have a follow-up question from the line of Christopher Yudi from SEB. Please go ahead. Hi, sorry. My question was just answered, so I'll I'm covered. Thanks a lot. Thank you, Sophie. No problem. And as there are no further questions, I will hand it back to the speakers. So thank you very much, everyone, and do not hesitate to contact myself, Anders or our IR department should any more questions arise. And otherwise, we'll keep in contact over the coming quarters, and thank you so much for joining this call. Thank you. This now concludes our conference call. Thank you all for attending. You may now disconnect your lines.