Earnings Call: Q3 2020

Nov 19, 2020

Thank you, and good afternoon and good morning. Marty Duvall, the Chief Executive Officer of Oncopeptides. And I'm joined today by Anders Martin Lauf, our Chief Financial Officer of this operational update based on our Q3 results here at OncoPeptides. Just a reminder at the outset that on November 30, we will have a Capital Markets Day, really looking forward to that, a deeper dive into our launch planning and key opinion leader feedback on Melflupin. We'll also have a post ASH call. So we'll let you know when we get that scheduled. If we can flip to the first slide, our Slide 2, just our disclaimer, asking that everyone please look at some of our statements online for balance and accuracy and correctness. I will be making some forward looking statements. So flipping to Slide 4. So as mentioned, my joining Onco Peptides back in July was a signal of the transformation of the company into a fully integrated biopharma company, and we're really excited about the progress we've made throughout 2020, but more specifically over the past few months that we'll provide an update on. So again, our focus in building this fully integrated biopharmaceutical company is to enhance our discovery and IND generation engine, our life cycle management of our products as they move through, focus obviously on melflupin, our lead program at this point in time. And then the final stool leg of the stool here in this transformation is our launch investment and the geographic expansion of our company has undergone significant transformation with a ramp up in the U. S. So we'll touch a little bit on the discovery and IND generation, some advances we've made to really show that we have a peptide drug conjugate platform and a second product that's moving into the clinic. Overall, with the melflupin development program focused on a very large and potentially profitable multiple myeloma market currently valued at $23,000,000,000 Very broad program. We'll touch on how we intend to use our clinical studies to expand our label and be able to reach more patients. We're in the midst of this priority review at the FDA with PDUFA date of February 28, and I'll describe for you where we're at in that process, and we're excited about progress and where we are today. And then thinking a little bit broader about geography, U. S. Launch on track. Market cap is moving in the right direction. Anders will talk to you about the cash position, and we'll talk more about our launch preparation. So moving to the next slide. We feel that we're reducing a lot of risk and generating value here at Oncopeptides and across the spectrum of this transformation. So first and foremost, with the Verizon data, outstanding positive results in triple class refractory multiple myeloma, derisking from a clinical perspective, our submission to the FDA and the acceptance by priority review obviously reduces our regulatory risk. Jacob moving into the Chief Scientific Officer and me coming in with a little more global commercial, commercialization experience, really derisk things from an operational perspective, not listed here, but we've done some expansion on the IND and drug discovery side with our investment in a new lab in Solna in Switzerland sorry, in Sweden, where we've significantly expanded our capabilities. OCEAN trial is fully recruited. We'll talk about that in a little greater depth. We've talked about Europe and our intent to accelerate things in Europe. So really looking forward to beginning that build. Sure, things on the financial side with a loan. And as I mentioned briefly on the prior slide, we've announced that 2nd product, 2nd candidate from our peptide drug conjugate platform has been submitted and IND applications have been submitted to the FDA. So good news there. We're now a platform play. And in 2021, we'll have 2 drugs in the clinic and a lot of things going on with melflupin, obviously. So next slide. I want to focus a little bit on what's really new and our focus on the commercial build that is underway. So really paving the way for a successful launch, and we've got a tremendous team that we've recruited to oncopepides. You see on the right hand side of the slide, our focus has been on bringing in people who have very significant launch experience, specifically in hematology and oncology. We also have a good blend of folks that have worked in the multiple myeloma space, understand that space, are well connected to the key opinion leaders in this area and those important relationships will be leveraged as we look to make sure that every patient that can benefit from nelflupine gets access and the opportunity to try nelflupine. More specifically on the people side, we had announced Mohammad Waddah as our General Manager of the U. S. Business. I've had the opportunity to work with Mohammed at several different companies and really trust and believe in his experience and expertise. And he's doing an outstanding job in leading our U. S. Team. Also had the opportunity to see Sarah Donovan, our Head of Marketing in action. She brings a tremendous amount of oncology, U. S. And global marketing experience. And she's built a tremendous team, has an outstanding relationship with our sales team, with our medical affairs team and has really made inroads and influences across our entire organization on the R and D side as well based on her expertise. And Doctor. Paul O'Connor, we're blessed to have someone with such deep hematology experience, both in academia, but also on the industry side, 17 years of industry experience, 30 overall years of oncology experience. And she's led the development and launch of several important programs. So really pleased that she's part of our company and playing such a key role. Next slide, please. So where are we? We've talked about and discussed in the Q3 report that we're building launch readiness in U. S. And our organization is set for launch. So what are the key things there that you should take away? We have a field sales team that's staffed and trained. As we had the PDUFA date for February 28 in our crosshairs internally, we were working faster than that and more ambitious and look to make sure we were launch ready in November. So we've made tremendous strides in building the team, staffing the team, training the team. So they're in house meeting and learning more about multiple myeloma and devising ways in which we can win for patients with nelflupine. Our MSL team has been onboard a little bit longer. They're now a full team, engaged with key opinion leaders and also community based oncologists and building the important relationships that we'll need to be successful. Market access, of course, will be important. We want to make sure that no patient is left behind as it relates to our market access activity. So we've done a tremendous amount of work, background work, working with payers to establish the relationships that are needed there. We think we're going to have a key interesting advantage, particularly in the COVID environment with our convenient 30 minute administration and the interest high interest in the utilization of doublets in resistant refractory multiple myeloma in the community oncology setting in the U. S. So the oncology networks and GPOs are really an important piece of that, and we're working hard to build the relationships to make for a smooth launch. Really proud of the customer information management system that we built. We really tried to make this state of the art. Here, we're tapping into resources on product utilization, on the managed care side of the business to make sure that the latest and greatest real time information is put in the hands of our field sales team, both our MSLs and our oncology account managers, to understand where the activity is going in terms of ordering the product, using the product, challenges with the product, so that we can be a resource to help make sure that things go smoothly. On the distribution side, our strategy set, product flow set, network established, patient advocacy, we're doing a tremendous amount of work and the relationships are strong. Medical information, a bevy of response letters and systems in place. We're going to have new data at ASH that will be incorporated into the medical information materials and responses. Our marketing materials, as you may be aware that as a subpart H accelerated approval product, the FDA will be reviewing all of our marketing materials. We finalize them. They're just waiting for us to drop in approved label. So those will go down to the agency. We put a lot of time and effort into our patient support services. Patients are the focus for us. They're our ultimate customer. So we've built a program that looks at access, helping patients with any prior authorization support that's needed, any denials, any benefit investigation that will need to occur, looking at affordability, co pay programs, free drug programs for the underinsured or non insured, we're funding furlough programs and adherence. So once a patient gets on the product, we're building in the support that is necessary for patients to make sure that they're receiving all the value they can from melflutin. And product supply launch quantities are built. We're awaiting the that label and shipping to the U. S. So a lot of details, and we'll come back to these a little bit more in the Capital Markets Day, but exciting progress as it relates to our launch readiness in the U. S. Next slide, please. To those familiar with our program and know our clinical trials, I won't go into too much depth on each of these, just pointing out some of the key points. The obviously, is forming the basis for approval of the product around the globe, starting with U. S. And then to Europe, the change in strategy there from a European perspective. We have been waiting for the OCEAN trial. And obviously, the OCEAN trial is a milestone that we really look forward to. As a reminder, this is a head to head comparison of melflupin versus pomalidomide in a lenalidomide refractory population. We've accrued close to 500 patients into this trial. We completed that accrual. We're in the process of tracking the events. It'll take 339 events to reach a point where we'll begin to have top line results, and we'll talk about when we foresee having the results of the OCEAN trial, but very important to us. ANCHOR is really, really another important trial for us. And for those that have reviewed the program for ASH in the next couple of weeks are aware that we have an oral presentation on ANCHOR. Happy to report that the team has done an outstanding job updating the data, a new data cut. So what you will see at ASH at our oral presentation or during that oral presentation will be a much more mature data looking at the important combination data of melflupin with daratumumab and also with bortezomib. And it begins to build that foundation for moving into earlier lines of therapy and making sure that we're maximizing the value that patients can get from melflutin through combination treatment. BRIDGE study is ongoing, highlighting our unique what we believe is a unique benefit based on the fact that renal impaired patients, we believe, can uniquely benefit without significant dose reduction. So we're continuing that study. Importantly, it's more than just multiple myeloma as it relates to melflupin. So we have a trial in amyloidosis, and we're actively, as we think about 2021, putting in some signal seeking trials in other hematologic malignancies that we think will be value creation points and also expand the opportunity to treat more patients outside of the diseases that we're currently focused on. Again, these value building opportunities are obviously important to all of us. Another Phase III trial, the Lighthouse trial combination with daratumumab, we're excited to get that trial started. And then PORT, as most of you are aware, is a open label small study randomized crossover looking at the central PORT cast delivery of melflupin that we've utilized in our clinical program to date compared to peripheral infusion. So looking to provide some flexibility in the way the product is administered. So an outstanding and deep clinical development program for melflipin that we look to add to in 2021 beyond. Next slide, please. When we step back and thought about the target product profile for melflupin and what would make this product a potential winner in the relapsedrefractory myeloma market and see how it stacks up on the left hand side of the slide. So as it relates to activity and that activity needing to be over 20%, we've delivered in the 2 early trials, the O12M1 and Verizon with response rates that are north of that target. Single agent approval, it's a key here in the oncology space. Even though there's a lot of combination use, it's important from a regulatory perspective as well as confidence from a clinician perspective that you prove that your agent as a single agent is an effective drug. So we do that in our single arm horizon trial, but also the OCEAN trial, that pivotal head to head study versus pomalidomide. And pomalidomide was selected because it's a workhorse in relapsedrefractory multiple myeloma. So establishing that our activity is equivalent or potentially superior to pomalidomide is the key in making melflupin a foundational product in the future treatment of multiple myeloma and moving it up in therapy. Synergy with other drugs, talked about the ANCHOR study, daratumumab, bortezomib, a combination in early stage disease is important. We've demonstrated good quality of life and we have a poster at ASH that will speak to this a little bit more related to the HORIZON trial. And I also touched on this convenient administration, this 30 minute infusion and how that's going to be helpful, particularly in the COVID-nineteen era where chair time is we're looking to minimize that, but still have patients coming into the oncology office, into the clinic, into the outpatient clinic on a regular basis to monitor how they're doing with their disease and how they're doing on therapy. So a lot of good feedback on the profile of the drug as it relates to that in the administration. Next slide, please. So here we link that clinical development program to opportunity. So Horizon, our anticipated label would be in triple class refractory population. We have unique call out of EMD patients, the extramedullary patients that are of high risk. So that's a 20,000 plus patient population. EMD expands that a little bit. There is overlap as many of the patients are later stage, these high risk patients and have been exposed to all three class of the drug. So it's a little bigger than just that triple class refractory population. The OCEAN trial, that head to head superiority study versus pomalidomide puts us in a different category, a little bit earlier in terms of the course of the disease and additional 25,000 patients when we look at the U. S. Market are patients that are treated with a single regimen, so not in combination. Now the ANCHOR and Lighthouse study move us to the final rung here of the circles. So important that we show that combinability, the benefit risk profile of nelklupin works with some of the other key workhorse agents in multiple myeloma, and we're doing that through the ANCHOR and Lighthouse trial. And that brings the opportunity higher to more than 20,000 additional patients. So pretty exciting out of the gate and building in the future with Ocean results targeted for the first half of twenty 21, we can see that working into our label in the near term as well. What does this translate into in terms of on the next slide, thinking about products, effective products in relapsedrefractorymultiple myeloma. So here we take a look at a rolling 12 month through Q3 of 2020 worldwide sales of products in the market. So clearly, a large opportunity. We see year on year growth across the spectrum of these products, ranging from as small as 4, but up to 37 percent growth on an annual basis, looking at daratumumab as a $3,400,000,000 drug in worldwide sales and growing at a pretty strong rate. At the bottom, you get a feel for 1st year sales of products in the category. So even at the lower end, we see sales in that $60,000,000 to $100,000,000 range. So exciting sales potential, exciting future potential as it relates to nelflutin in relapsedrefractory multiple myeloma. Next slide, please. So I alluded a little bit to ASH, and it's an exciting way for us to end the year. Product approval would be another exciting way to end the year. But certainly, here we know the data that's been accepted, the new data that's been accepted for presentation at ASH. We think it really validates the strength of our peptide drug conjugate platform. So 12 data presentations have been accepted. The hallmark here or the key that we're most excited about is the oral presentation of the ANCHOR study. As I mentioned, that is based on a later data cut. So stay tuned for some very interesting data, updated data of melflupatin in combination with daratumumab and also bortezomib. There's also some interesting posters. So we get a lot of feedback from key opinion leaders as we look at the RISE and study, how did you do specifically in elderly patients? What about the high risk cytogenetic patients? There are patients that I believe could benefit from nalflutin. This extramedullary cohort you mentioned is 42% of the horizon. How did the product do specifically in that area? If you're talking about melflupine that delivers an alkylating payload in a unique way through this peptide drug conjugate, How did the product do in clinical trials against patients who had prior alkylating therapies? 1, 2, 2, alkylators. And we answer all of those questions at ASH in these unique posters. And by and large, the conclusion is risk benefit profile that we see across the entire Horizon study also rings true for these unique categories. So take a look at that at ASH. And again, we'll probably have a webcast soon thereafter that we can dive a little bit deeper. And also some important signals as it relates to quality of life and quality of life analysis on patients who have been in clinical trial for melaflutin. And we're also committed again to continue to build a differentiated profile and continue to products. So we'll continue this investment in areas that demonstrate this differentiation of melflupin. So specifically, multidrug resistance in certain models based on prior drug exposure or resistance, carfilzomib, bortezomib. Also some interesting preclinical work that may speak to why from a quality of life perspective, we may be getting some good feedback as it relates to pain through this osteoclastogenesis poster that is being presented. So very exciting stuff from both clinical and preclinical perspective at ASH. And really, a nice way to cap off the year as we've been monitoring and building how we're growing the awareness of melflupin from a pre launch perspective in the U. S. And monitoring based on the evolving profile of the drug, the percentage of physicians who claim that they would be very likely or likely to use nalpifen in their patients. So good trends as it relates to awareness. We certainly look forward to the January time frame where we can reflect back on that large ASH presence to see how we continue to move the needle on that and also grow interest in utilization of the drug. With that, I'm going to turn it over to Anders to provide an update on the financial side related to Q3. Thank you, Marley. If we then turn to Slide number 15, you see an overview of the financial results for the January to September period for 2020. And as you can see, the operating loss increased to SEK 1,079,900,000 for the 9 month period. That's quite an increase for some SEK495,100,000 for the same period last year. If then if you look at the quarter, the loss was SEK383,500,000, up from SEK 189,600,000 compared to last year. Quarter by quarter, the loss is actually lower in the Q3 than in the Q2 when the loss was roughly SEK 399,000,000. So R and D costs are down a little bit for the overall quarter, whereas marketing and sales is continuing to increase. Going back then to the 9 months figures, looking at R and D work, as you can see, the R and D cost increased from SEK391 1,000,000 to SEK630 1,000,000. This is primarily driven by an increase in clinical and private supply that was $470,000,000 for the 3 months period and the biggest contributor here is the OCEAN trial where we spent SEK 246,900,000 for the 9 month period. Roughly SEK 107,000,000 after that was down supply. So we spent a lot of money on this for the 9 month period. 2nd largest trial is the Horizon trial where we spent 49,000,000 dollars Marketing and sales costs went up from $1,000,000 last year to the $282,900,000 this year. This is of course driven by the buildup of the and sales organization in U. S. The tool cost for our U. S. Subsidiary was roughly €209,000,000 Not all of that is reported in the marketing itself, €61,000,000 is reported in the admin line. Another spectacular figure is the number of coworkers that increased during the period. We have grown tremendously like 200% of the year going from 73 people as of September 30 last year to 232 this year. Almost half of those are now in the U. S. Subsidiary, we're continuing to grow there during the Q4. Cash flow for the January to September period was negative SEK939 million. For the quarter, it was SEK340,000,000. Cash flow, the negative cash flow will continue to increase a little bit towards the end of the year, so we are expecting somewhere around SEK 400,000,000 in negative cash flow for the Q4. So cash position was SEK 1,251,600,000 as of September 30. This was an increase that we concluded the generated share is SEK 1,400,000,000 in July. This number does not include any funding from a loan facility that we secured with the EIB in October. That's a €40,000,000 loan facility that will be available to us based on us reaching certain milestones relating to the commercialization of Mediaset in 2021. With that, I leave the word back to Marty to control the news flow for the remainder of the year. Thank you, Anders. So we have here projecting out into 2022 some highlights from a news flow and major milestones. So in green, you see things that we've accomplished in the past couple of quarters. So really excited about, again, hitting on the milestones and providing that news flow. Few things remain here in 2020. Publication of the Horizon data in the Journal of Clinical Oncology, we're in the final stages of that and expect that, that will be published in still within the calendar year. So really important for that to be part of what the sales force has in demonstrating the benefit risk profile of Verizon. The Capital Markets Day, as mentioned, November 30, so stay tuned on that one. Look forward to that deeper dive on the clinical program and KOL feedback on nelflutin, the multiple myeloma landscape we're launching into. So we think that'll be a pretty exciting program. Anchored data at ASH. And as mentioned, we'll talk we'll likely have a webcast to kind of review some of the data in-depth that I hit at a very high level on the ASH slide. Looking into Q1 of next year, again, OPD5 sister analog to noflupin. This is a different formulation, different and a new chemical entity that would be focused on the stem cell transplant area. So we're really looking forward to that. The formulation enables us to deliver in a convenient way, we believe, higher doses of product that can possibly impact these stem cell transplant patients. So early days in that program, but we're certainly looking forward to getting first patient in, again, showing that we have a real platform in the peptide drug conjugate platform and the second product in the clinic. Results from PORT, the potential approval and launch in Q1 from an EU perspective. Moving forward with our work towards gaining approval, the top line results on Ocean. So as we track those 3 39 events that I mentioned, we believe that we'll have those we'll have reached the magical event number in time for disclosure in the first half of twenty twenty one and would target having top line results hopefully at the ASCO meeting. Then we'll move to the European hematology meeting, anchored more data, BRIDGE study that I talked about. We'll have an update there. And then thinking even further out, it's about translating that ocean data into labels in the U. S. And in Europe. So exciting news flow as we move forward. And again, I think a really strong quarter, really proud of the team and how we're able to operate in what is a challenging time globally for us regarding the for everyone regarding the pandemic. But we continue to be focused on delivering to you, our shareholders and delivering to the patients. So with that, I'll turn it back to the operator for the Q and A portion. Thank Our first question comes from the line of Victor Sundberg from ABG. Please go ahead. Yes. Hi, and thank you for taking my questions. So three questions from me. I noticed that you expected a readout promotion, as you said, in the first half of twenty twenty one before, but now you communicated in quarter 2 in 2021. Any reason for that? Why you can we get a more detailed time line? Are patients still going longer than you anticipated without an event in the study? Or what's the reason if you could give some more flavor on that? Well, I don't think there's a real change there just being slightly more definitive. Obviously, as you know, as the events come in, that triggers a lot of work that needs to be done on the clinical operations side in terms of data cleaning and scrubbing and verifying results, quality assurance checks and those things typically take a few months. So as you as we proceed with time, we're able to hone in on that being us feeling that this would more concretely be in the Q2. I think we had talked a little bit about generally the concept you're talking about, about patients perhaps staying on drugs longer, which of course is a very positive thing from a patient perspective. No way in which we can determine how that impacts one arm versus another, but good news overall for patients. But there was no intent to signal anything any different than just the normal process here of reaching the events, cleaning the data and having it available. Okay. Yes. Thank you. And with regards to DASERV, you showed of around 100 doctors. It seems like a lot of doctors want to use the centrifugal as refractory patients. But maybe an extramedullary disease, did you anticipate a higher response given your data? Or should we read it as doctors aren't yet aware of your data in that subgroup? And also, did you get any comments as well on how physicians are viewing your drug, not only yes or no answers that you could share? Yes. No, good question. So I would say on the EMD, it is related to the specificity of understanding and knowing that data. We don't we're in a situation right now where there really aren't kind of regulatory standards and key definitions and parameters that are universally agreed upon that designate whether a patient is extramedullary disease patient or not. I believe this will grow over time. I mean, as we're we don't have a final label and approval. We're not sure exactly how EMD will be handled in our final label. Certainly, if there's any type of call out, we would expect that we would be able to move the needle here. I think overall from a feedback perspective, we get good feedback. We get feedback that this product the profile is very interesting. The results are compelling. We know it's a crowded field. We know there are a lot of exciting things going on. We hear because of the time frame that we're launching in, right, and other products with similar labels in the triple class refractory population, There's immediate thinking about the malslutin benefit risk profile relative to exovia, which I think by and large, as you would expect, our product is seen as a product that is more tolerable, appears to be equally as efficacious. And there's a preference towards the convenient 30 minute infusion. So we get good feedback on those parameters as one thinks about some of the other choices and selinexor being 1. And also with the launch of belantamab, we're early days related to belantamab. Of course, the BCMA target is one of interest and will continue to be of interest as we look at the approval and continued growth in thinking about the CAR T type therapies. But as it relates to blintamab, a challenging product to use, particularly in a community setting with the need for the ophthalmologic kind of consult, these visual acuity, very unique adverse event profile. So I think it's when it comes to the non hematologic toxicities, which from a melpalupin perspective, there's pneumonia at fairly expected rates when we look across products. The cytopenia issue is an issue that oncologists, hematologists are used to dealing with. And there are no other large outliers on the non hematologic toxicity profile. So it's pretty expected and a product that they think is will be quite manageable, that is delivering efficacy that appears to be durable in patients of high unmet need. So early days regarding moving the line here and influencing the very likely and likely to prescribe, but we're encouraged by the numbers. And it's pretty typical, right, to see this type of flipping back to Slide 13 in a stepwise fashion in terms of use in earlier patients. We know there's more work we need to do on the clinical development side to move the product up in therapy and some of the keys there being that OCEAN trial, the direct head to head comparison and also the combinability question. So hopefully, that helps a little bit, Victor. Yes. And one final question here as well. So on one of your abstracts, you showed some more data on patients on previous alkylator therapy. But I kind of missed the subset of patients that were refracted to Melkalon, not only exposed. Will we get some more flavor on that specific group, the melpalone refractory patients on ASH maybe? If you could comment on that. Yes. I think look forward to hearing a little bit more about that, and we certainly can tease that out for the Capital Markets Day as well and post cash. So yes, that's an important component for us. So thanks for the questions. Okay, perfect. Thank you very much. And the next question comes from the line of Christopher Nudy from SEB. Please go ahead. Hi, there. Yes, I just had some questions on, first of all, just sort of housekeeping. Should we expect much in the way of remaining costs from Horizon? And then on clinical development, what obviously, you're going to need to do more combo trials to keep driving sales and broaden the label of melflefin once it gets approved. So other than Lighthouse, when and what the when could we expect that you would announce new trials and what do you need to see before you do it? And also, let's say, I guess, it presumably depends a bit on what the FDA decides to do on the label now. But with respect to EMD, do you have any plans to add to the clinical data for that subpopulation specifically? Thanks. Yes. Thanks, Chris. I'll take them and if you need follow-up or I need clarification, I'll certainly come back to you. So on the horizon, I mean, the good news is there's we're continuing to follow some patients, but those costs are obviously coming down. I don't know, Andres, is there anything specific that we can provide at this point in time related to that? Yes, sure. So for this year, I think Horizon will be sort of in the $60,000,000 range for 2020. I think you should expect that to go down to roughly half that into next year. Okay. And then on the clinical development side, yes, we're with you in terms of more combinations needed. My understanding is the ANCHOR trial, the way it's built, we have the opportunity to open up other cohorts of patients. The focus out of the gate has been on the combinations with daratumumab and bertesimab. So that affords us the opportunity to look at some of the safety efficacy issues in a Phase II setting with those combination trials. And as you mentioned, Lighthouse is one where we're moving into a Phase III setting. We're certainly kicking around internally and getting feedback from key opinion leaders on what's next, another effort in terms of combining melflupin with a backbone agent in the multiple myeloma space. As we kind of finalize and hone in on our 2020, 2021 operational plan, I think as the year unfolds, you'll get a little bit more guidance on where we intend to go relating to those future studies on melflupin. We're certainly not done as it relates to relapsedrefractorymultiple myeloma. And as I alluded to in some of the opening remarks, the other considerations and of course, these are much, much lower in scope from an investment perspective would be smaller Phase 2 single seeking trials in indications that are beyond scope of multiple myeloma. So kind of building on our platform in multiple myeloma amyloidosis and then a couple of other e malignancies. So I'd say stay tuned for early days in 2021 once we finalize the budget and plans and prioritization. Balancing again, we it's exciting. When you look at the transformation of the company and you think about it from the platform and the platform delivering with multiple products, life cycle plan and a lead program that from a preclinical perspective, we have activity across a range of tumor types. And then thinking about the commercialization front and the opportunities in the U. S. And Europe, a lot of places where we can invest capital. So it's exciting. Some of those choices are tough choices, and we look forward to making them and disclosing them as we move into 2021. So yes, and your final point regarding extramedullary disease patients. So we do and do put into our kind of portfolio of trials on nelflutin in the EMD trial. I think we are in some ways waiting to see what happens from a label perspective. But we certainly believe that more evidence in that patient population can be helpful in establishing a unique and differentiated profile for the drug. So it would be money well invested on that front should we get positive data in EMT patients. Yes. Okay. Thanks. And I mean, I guess following on from the earlier convo question, I mean, I guess one thing we were wondering about is whether sort of something along like a conceptually an Ocean 2.0 where replacing not just sort of as a single agent, but replacing the combo backbone and targeted agent type of concept. So instead of continuing with VR and something else, head to head of VR or whatever it would be and versus Y Gallo and one of the other newer products like Belemaf or I don't know what. Is that so that seems like a place where you might be able to show superiority with the same number of drugs again. Yes. Interesting thoughts, Chris. Really appreciate your engagement and thinking along those lines. And I've had the opportunity over the past since I joined to kind of get a sense from key opinion leaders prominently in the U. S. And Europe and their thinking and certainly they mentioned some of the things that you're describing. So appreciate that thinking and certainly get back to you as the program evolves. As we commercialize it, it becomes more interesting from the standpoint of there's access to drugs in these cooperative groups that have interesting ideas, interesting studies, investigator sponsored trials. Obviously, you would expect our medical affairs team is has opened up such a program globally and in the U. S. With areas of interest and certainly combining and combining with new products looking for differentiated signals would be part of our interest in looking to make nelflefin even more effective for more patients. So we're certainly thinking along the same lines. Okay. Thank you very much. And the next question comes from the line of Boris Peaker from Cowen. Please go ahead. Your line is open. Good morning, Marcus. Good morning, where you are. Two questions from me. First on the regulatory perspective, I'm just curious, where is the drug manufactured and has the FDA conducted the required site inspection? And second, just thinking commercially about nalofen, do you think exfoli will provide a good launch trajectory that we should use as a reference? Yes. So, Anders, can you remind me on the manufacturing side, it's just not top of mind? Yes, sure. Yes. So it's the drug is produced at Cenexy in Belgium. Drugs are in Sweden. Both of these sites have been reviewed or audited by the FDA recently. So we do not expect any problems from travel restrictions or anything regarding in that aspect. I think that answers your question. Okay. And then another question Yes. The exfoliovo trajectory. Yes, I think it at a reasonable level. I mean, there were some challenges. Obviously, the what we hear played back to us is that, that drug at its indicated dose had some challenges and patients came in, the non hematologic side effects are an issue. Physicians are working around trying to make the drug more tolerable through dose reduction. We see more data coming out, the BOSTON data and an sNDA in review to try to capture the positive benefits of that mechanism of action. Each drug that launches, launches into a market, I always characterize as different than the one before it. So certainly, what we're launching to is a little bit different than what we launched into. They launched into a market where they didn't exist and certainly belantamab didn't exist. So we launched into a market where there are 2 other choices. We believe we're the stronger choice based on benefit risk profile, but you'd expect that of us, I'm sure. There are other activities that are ongoing in the marketplace that are exciting, exciting with respect to patients. These patients are getting many lines of therapy. We've kind of shown overall as we look at survival is improving, it's moving more towards that chronic disease stage. But there seems to be ample opportunities for more products to be utilized that work in different ways. So it's a matter of where you fall in the sequence of that treatment in a at the outset in the marketplace. So I think it's reasonable. Obviously, I'm hoping we do better. Great. Thanks for taking my questions. And the next question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Hi there. Thanks for taking my questions. Just regarding the European filing or the decision to file in Europe, Did you have discussions with the agency ahead of that decision? And then just given that Carifarma struggled to get approval in Europe, what drives confidence that you will fare better? Yes. Good question, Lucie, and good to talk to you again. 2 days in a row, right? Yes. Yes. Really, really good question. So the intent to file and our announcement on this intent to file was just based on our read of what it takes to be in the category that would make it acceptable. Our original strategy was to utilize the OCEAN data, Phase 3 comparative data. We saw that valentumab had moved forward positively with their submission, a data set of similar scope. Same from a Karyopharm perspective initially, although they have not achieved the milestones that and progress that have been achieved by valentumab, which is now approved. It appears that perhaps the BOSTON data will play a role in the eventual European approval of selinexor. So I think if we think back to the FDA review, right, it took an Oncology Drug Advisory Committee meeting and discussion on selinexor prior to FDA getting comfortable. We've gotten signals back or as we mentioned, we got signals back from the FDA that we would not require an ODAC. Our so the short answer to whether or not we've had discussions is no. It's based on our belief that we fit the profile, we fit the we check the boxes that are necessary. And the way we stack it up against the competition, we believe that we can get that conditional approval. I think the one challenge that we keep in mind as we think about the process from a European perspective and the timing of the OCEAN data, would that potentially cause some type or have some impact on the time line, and it very well could. We haven't specifically guided around that because we don't quite know ourselves yet as the OCEAN trial is PFS dependent. So discussions ongoing with the agency, positive progress, but prior to the intent to file, there was no discussion. I hope that helps. Very helpful. Thank you. And the next question comes from the line of Erik Gunuschon, who's a private investor. Please go ahead. Hi. Thank you very much for taking my questions today. I have 2 actually. The first one is, I wonder if you could comment on the budget, the current budget versus the original budget for the OCEAN study. Has it become more extensive due to the higher amount of pomalidomide? And my second question is, a new PAM data was released in Janssen's 2020 ASH abstract for the PAL study. For example, the PAM plus dexamethasone arm had a PFS of 6.9% with an ORR of 20%. You have a view on how to interpret these results in relation to the palm arm in the ARRUM study? So I'll let Anders handle the first question related to the budget. Right. So yes, thanks for the question. Yes, we have communicated that the patients are seeing longer on OCEAN trial. We believe that's a positive sign. Basically, that gives us an indication that the investigators like the treatment and are putting healthier and healthier patients on trial. We don't know of course what arms are you see the difference of the PFS response in. And yes, we have patients that have stayed on trial for a long time. So that has increased sort of the average time that each patient is on PAMA. So hence, we have on that. That's one minor. We have also had a large effect where we have had to buy a lot more families due to the COVID-nineteen pandemic. So we have to send out to all of the sites in advance to ensure that the trial would continue. Another factor that has increased the cost for pilots during the year that we have simply made the trial bigger. So it should have been more efficacious. Now we increased it 295. So that's also a factor to why the cost has not for POCOMALYST compared to sort of initial budget. But you cannot draw any conclusion from what the end result would be on the increased pharma list cost. That is not something that you can do. So there are a number of factors interfering here. So I hope that answers your question. Yes. Okay. Thank you. Then maybe regarding the second one, I haven't done my full ASH homework yet, focused on ours. Certainly, the way in which the OCEAN trial was built was a look at patients of a particular profile, lung refractory patients within a certain period of time and our deeper view of the data that those patients were negatively impacted in terms of overall response rate and PFS. So certainly, as we provide perspective, thinking forward to our post ASH kind of review, we'll work to put data competitive data into perspective. And hopefully, it will help at that point in time. I would say as we look at ASH overall, it was a team and talking about the execution, the fact that a company growing like ours with respect to people and geography and the milestones that were achieved, we're really proud of the scientific excellence in both quantity and quality for our showing at ASH, and we look forward to putting that into perspective relative to the competitive data at a future call. All right. Thank you. And we have one more question from the line of Rene Rauters from Kempen. Please go ahead. Yes. Hi, guys. Congratulations on the progress and thank you for taking my questions. In line with an earlier question on the European pathway for approval for mefloquine, what are your plans for potential marketing? And also taking also taking into account your current cash runway? Yes. Thanks, Renee. I mean, right now, as we look at it, we're operating with the intent that we can do this alone from our vantage point in Stockholm, with the company's headquarters, the talent that we have there, complementing that with some of the positive experiences that some folks on the team, including myself that have had regarding a European build in the hematology space, the engagement that we have from key opinion leaders in some of the key countries and beyond or some of the top countries and beyond, we feel that overall value can be maximized at least from our vantage point today in a go at it alone. As I kind of mentioned in answering one of the earlier questions, we do have a lot of choices to make and that's where you want to be with respect to the early stage products, new products, our melflupin clinical development plan and expanding beyond the current indications and then the geographic footprint. Certainly, beyond Europe, we would be thinking in terms of partnering. So Japan is obviously a territory that would come to mind for all, being the 2nd largest country from a pharmaceutical revenue or opportunity perspective. That's not a geography that we would see ourselves putting feet on the ground and look for partnerships. So there are ways in which we can utilize geography and leverage the data that we've generated in trials like Horizon and Ocean to bring in more non dilutive capital that can help us avoid having to build a footprint in some countries, but also put more fuel in the tank from an R and D perspective. All right. That's helpful. And then one last question from my end. So with the IND for OPD5 submitted last month, can we expect more molecules from your PDC platform to enter the clinic in the near term? Entering into the clinic in the near term, that's a good question. I don't want to specifically guide that. We don't comment a lot on obviously, on things that we're kind of working on. OPD5 is an interesting one. We do see an opportunity to again leverage the innovative science that we have and the talent we have to generate new products. I think it might be a stretch to get another product in the clinic in one calendar year, but certainly, we would hope to have some development candidates that we would have in mind towards the end of 2021, but no specific guidance on that at this point in time. All right. Thanks a lot. As there are no further questions Great. Well, super, super. Well, thanks to everyone for your engagement, continued interest, and we look forward to our engagements at the Capital Markets Day and beyond. So have a good evening. Bye now.