Y-mAbs Therapeutics, Inc. (YMAB) Earnings Call Transcript & Summary

Good afternoon, and welcome to the Y-mAbs Therapeutics KOL Webinar on DANYELZA frontline and HITS data in high-risk neuroblastoma. At this time, all attendees are in a listen-only mode. A live verbal question-and-answer session will follow today's formal presentation. This webinar is not being recorded, and there will be no replay made available following the conclusion of today's event. I would now like to turn the call over to your host, Thomas Gad, Chairman, Founder and President of Y-mAbs Therapeutics. Please go ahead, Thomas.

Thank you, Sara. Before we begin, let me just remind everyone that today contains -- today's discussion contains forward-looking statements as defined by the Reform Act of 1995, the disclaimers here. With that said, we are very pleased today to have Dr. Jaume Mora from Hospital Sant Joan de Deu in Barcelona, probably one of the biggest sites in Europe treating high-risk neuroblastoma, among other cancers, a really developed pediatric center. And he will be talking about his experience of frontline with DANYELZA, and he's also one of the only KOLs who experienced treating both with Unituxin and DANYELZA. After that, we'll be joined by Dr. Modak, who's treating a very difficult-to-treat group of patients that are not responding in second line, which is his protocol. And after that, we will hear from Dr. Steen Lisby, our Chief Scientific Officer, who will give us an update on the very exciting SADA tech platform that we are working hard on. And last but not least, our Chief Executive Officer, Dr. Moller, will give a company update. And with that, we are very pleased to introduce to you Dr. Mora. Thank you very much.

Sorry, am I going on first? This is Shakeel Modak. Or is it Jaume?

You can go. Jaume first.

Okay.

Sorry, Dr. Mora is going first.

All right. Let me know just -- okay, here's Jaume's slide, so he can go. Great.

All right. Well, hi, everybody. Thanks for the invitation. I'm happy to share with you our most written experience summarizing what we've learned over the years of using DANYELZA in first-line therapy for high-risk neuroblastoma patients in Barcelona, pediatric cancer center in Barcelona Hospital Sant Joan de Deu. Next, this is my disclosure, basically been consulting for Y-mAbs for quite some time over now. Next, well, for the general audience, I would like to introduce you what is high-risk neuroblastoma. We're talking about a very hard-to-treat disease. This is a disease that presents mostly before five years of age of life. It presents in many different ways. Here, it has shown a significant new filtration of the skeleton, the whole skeleton actually, it's bone disease, which can be seen in this MIBG scanning, which is what we routinely used to evaluate these patients. Patients can present in many different ways, fever, limping, bruising and even abnormal eye movements or abnormal sight. So it's a very systemic disease that it usually affects the child very much when they present. Next. Well, as you can see, this is the summary of many decades of work since the 1960s. Basically, that used to be an incurable disease, which using conventional therapy, and that includes surgery, conventional chemotherapy and radiation. So not until very recently, we were lucky enough to have our kids, our patients, survive of this disease. Next. So for -- again, the general audience and the context of my talk, the general plan of multi-modality management of this disease after many decades of research has come up to a general consensus of how we deal with these patients. In general, patients are coming in, and they receive what we call induction chemotherapy, several cycles of intensive multidrug protocol of chemotherapeutic agents, followed or together with or along with surgery of the so-called primary tumor. This usually takes six to eight months of completion, followed by the so-called consolidation phase, which classically includes autologous bone marrow transplant or stem cell transplant plus radiation therapy and followed afterwards for what it has been called maintenance phase, which includes the immunotherapy antibodies, most recently cis-retinoic acid in the past now mostly used in combination. Next. First, the induction therapy for these patients, how important is this? Well, we've learned that, certainly, chemotherapy and surgery are truly important in order to improve the outcome of these patients. So after induction, patients usually are evaluated. And according to the response to this induction phase, then we can correlate with the final outcome. So, induction therapy has proven to be significantly important. Next. As you can see here in this slide, I summarized for you decades of experience by many different groups and cooperative groups, nationally, internationally. So where you can see the complete remission, meaning every sight of disease that has been taken care of by the induction treatment, meaning everything is gone, complete remission after induction, clearly correlates with an increased five-year overall survival. So having a complete remission after induction is certainly important for the outcome of these patients. Next. Here, for instance, you have a most recent example of a cooperative trial from the German group. This is the NB 2004 protocol, which runs from 2004 all the way to 2016. This is the -- actually the last of these cooperative trials that run without any immunotherapy included, so the so-called standard management or conventional management. And as you can see, the outcome of these patients are still really very poor, with event-free survival around 25% and an overall survival which doesn't reach 45%. So we are talking about a recent -- most recent example of what conventional treatment of these patients can provide to you. Next. And the question then is why we fail the -- to cure high-risk neuroblastoma. As we said, and as I showed, induction chemotherapy is quite effective in -- and together with surgery, they have been shown to be significantly relevant to get the patients out of any detectable disease. So this is what we call gross disease. But we know that all these patients are left behind with so-called minimal residual disease or non-detectable disease, which eventually is going to grow back and cause the relapse of the disease and eventually the refractoriness of the disease and the death of the patient. So next, there are different -- there have been different strategies to manage these so-called minimal residual diseases. The first was in the 1980s, late 1980s and '90s. Well, people thought, well, if the disease is certainly sensitive to chemotherapy, why not provide higher doses of chemotherapy and use strategies like stem cell -- bone marrow, stem cell hemopoietic stem cells to rescue these toxicity. So then we can get a higher efficacy of our conventional cytotoxic drugs. Next. So that was certainly as shown as a paradigma of this strategy, the publication in 1999, more than 20 years now ago of randomized study major -- by the major competitive group in the United States. Next, in the most prestigious journal in medicine, next slide, and this trial, actually, if you go and look carefully, they randomized patients to high dose chemotherapy, but also with those drugs -- previous slide, sorry. With high-dose chemotherapy plus also TBI, which is total body irradiation. So what you use to kill all the neuroblastoma cells is significant, and it is relevant. So nowadays, this is no longer accepted as a strategy to kill neuroblastoma cells. So, all the strategies of high-dose chemotherapy are not the same. So, all the high-dose chemotherapy and transplant strategies should not be compared to the same or similarly. Next, the results of this trial were published, and there were -- it was apparently clear that high-dose chemotherapy and transplant plus the retinoic acid showed significant event-free -- improvement in event-free survival, which is the top red line. And that was really a landmark paper that was clearly followed by all the studies subsequently, in next slide, by different groups also showing any improvement of what seem to be an improvement of event-free survival. However, 15 later -- 15 years later of this -- that seminal publication, the same group, the COG group had to retract, and they wrote a letter of explaining that neither myeloablative therapy and stem cell rescue nor cis-retinoic acid after consolidation therapy significantly improved overall survival of this patient. That was -- there was an error in the statistical analysis, which was discovered actually 15 years ago, and that was -- that made a big impact in the field, certainly. Next slide. So in summary, I show you here several -- the summary of the different studies that have been performed in high-risk neuroblastoma randomized trials, showing that, yes, intensive induction chemotherapy improves event-free survival, yes. Stem cell transplants seem to be improves event-free survival, but neither of them improve overall survival. So meaning patients can -- will relapse, but it will relapse later as compared to conventional chemotherapy, but eventually patients will die. So, not improvement in the overall survival of these patients. Next slide. So the other strategy that was devised also in the late 1980s was the use of immunotherapy. Anti-GD2 immunotherapy was also tested in order to see whether they can take care -- took care of the minimal residual disease after conventional induction chemotherapy and surgery. Next. So this is the first ever publication on the discovery of anti-GD2 antibodies by Dr. Nai-Kong Cheung, who is the pioneer of naxitamab, DANYELZA, and he discovered the anti-GD2 antibodies to be significantly released when he injected neuroblastoma cells into the mice. So that is the origin of all the studies that came later on. Next slide. So after two decades of studies, we now know that how these antibodies work, actually anti-GD2 antibodies attached to the antigen on the surface of the membrane of the neuroblastoma cell, which expresses very highly the GD2, actually the highest expressing tumor cell of any tumor type. And then this antigen antibody releases a signal, which activates the granulocyte-macrophages, NK cells and so all these effector cells of the immune system of the child, which activates -- which get activated as well as the complement to kill the neuroblastoma cells. So here, we have the antibody plus the effector cells as the key points in this strategy of managing minimum residual disease. Next slide. So it was actually the Memorial Group who proved sequential studies that show the addition of murine-free antibody, the anti-GD2 antibody discovered by Dr. Chang, adding it on to the same schema of induction chemotherapy and early surgery actually improved the overall survival, the cure rates for first time above beyond 50%, which had never been shown before. And actually, several improvements, including the addition of GM-CSF, injected subcutaneously increased amazingly the five years overall survival of these patients getting into first complete remission after induction up to 80%. That was really striking observation that went on to be tested by different groups. Next slide. Until -- well, actually, this same group from Memorial, they actually looked back and asked themselves whether in the era of using anti-GD2 antibodies, whether the stem cell transplant strategy would have any impact. And certainly, they showed that there is no difference in the overall survival of their patients in a large group, whether the patient had received autologous stem cell transport or not. So that was the very first indication that in the era of anti-GD2 antibody most likely -- high-dose chemotherapy and stem cell transplant actually is not necessary anymore for the management of these patients. We'll come back to this in a minute. Next slide. So nonetheless -- and despite the recognition by COG that the data was not correct, the transplant -- the stem cell strategy transplant has remained in the overall management of these patients, surprisingly enough. So we're still dealing with data that comes in the literature that comes from studies that are using both stem cell transplant plus the anti-GD2. Next. And this is why we need to take this into account when we read the literature and the next New England paper of a randomized high-risk neuroblastoma from the COG, it was published in 2010, 10 or 11 years later from the previous one, and they tested actually the anti-GD2 antibody using Unituxin after the complete remission achieved after a conventional strategy, including autologous stem cell transplant. So this is data of event-free revival and overall survival improvement of immune -- anti-GD2 immunotherapy on top of stem cell transplantation. Next slide. So the SIOPEN Group, which is a cooperative group in Western Europe, also have shown that the post stem cell transplant plus their version of the chimeric 14.18 antibody, meaning that dinutuximab beta or QARZIBA also showed similar overall event-free survival rates at around 60%, similarly to the COG data from the New England paper in 2010. Next slide. All these non-randomized historic -- compared to non-randomized historical controls, they claim to have improvement both in overall survival as well as event-free survival again similarly from the COG data, but also post a stem cell transplant management in first-line complete remission patients. Next slide. So the summary of all these trials, adding these most recent Unituxin randomized studies of immunotherapy, they showed for the first time ever an improvement in overall survival of these patients. So immunotherapy, at least Unituxin, post the stem cell transplant was shown to be, for first time, improving overall survival of high-risk neuroblastoma. Next slide. Next slide. Okay. Well, in our experience using both Unituxin as well as naxitamab, we did a similar study from the Memorial looking back to patients, whether they had received the transplant -- the stem cell transplant or not. And next slide, we also reproduced the Memorial data showing that there is no statistically significant difference in the outcome of these patients. So in our earlier experience using both either Unituxin or naxitamab in first CR patients, again showing that there's no difference in the immunotherapy era for the use of stem cell transplantation. Next slide. So as I said, the question is, do we really need stem cell high-dose chemotherapy management in the anti-GD2 immunotherapy era. Next slide. And this is what we try to address with this simplified schema of management that this is what we provide to our patients nowadays. So patients would come in after induction chemotherapy and surgery received in their own institutions. We will thoroughly evaluate. And if the patient would be in complete remission, meaning no evidence of disease, then patients would go on to consolidation with naxitamab and GM-CSF plus radiation therapy, but -- and now stem cell -- high-dose chemotherapy and stem cell transplant. Next slide. So that is the -- this is what we've done together with the Y-mAbs, all through the last three years. Next slide. And this is what I'm going to summarize for you in my final part of the talk. So patients would come in, evaluate it, and then if in complete remission, they would go on to either compassionate use or future Y-mAbs trial formally to treat these patients. Next. So as I said, full evaluation would be a full bone marrow aspirate, MIBG and/or FDG-PET and whole-body functional MRI, just to make sure that we don't have any evidence of disease. And since June 2017, when we started using systematically naxitamab in our center, we have treated 73 patients, 55 in first complete remission, 18 in second complete remission, meaning patients had had a previous relapse, which was managed again to get back into a second complete remission, and then those patients would be managed similarly. Next slide. So this is what we called the full evaluation, MIBG should be completely negative, no evidence of skeleton or soft tissue disease. This is the dream of any family with a child with neuroblastoma to have MIBG negative scan. Next slide. Also, we use a whole-body functional MRI to evaluate, and we've shown that this is to be -- this is a technique that we've developed that it's fairly useful to evaluate residual images, scar images of previous sites of disease that you can actually measure the restriction of the water in these sites and have an index of restriction what is called ADC that helps to evaluate whether that particular lesion seems or not to be active. So this is a full-body MRI also performed in all our patients. Next slide. Besides bone marrow evaluation, so if the patient is found to be in complete remission, then patients go on to receive treatment with naxitamab and GM-CSF, established with 10 days continuous subcutaneous infusion of GM-CSF. First five days at 250 micrograms, next five days at 500 micrograms per meter square per day. Together with three doses of 3 milligrams per kg per dose of humanized-3F8 or naxitamab or now DANYELZA. This is what we called one cycle. And this is treated -- the patients are treated as an outpatient. Next slide. So patients would receive, if in CR, in complete remission, these five cycles of antibody plus GM. And in our experience, 16 out of the 73 were not able to complete treatment as planned, five because of significant toxicity and 10 because they actually relapsed earlier than planned. So, six out of the 55 increased complete remission, four out of the 18 second couple remission. Relevant toxicities that have been displayed and described, antibody related apneas, stroke -- one stroke that seemed not to be related to the antibody, but was a reason to exclude the patient. Next slide. This is the study that has recently been reported in the medical literature, showing the overall survival and event-free survival for the whole group. Next slide. And I'm going to detail you the difference -- significant difference of two-year event-free survival of 74% for first complete remission patients as compared to 38% for second or more complete remissions, meaning patients that had previous relapse are in higher risk of further relapses even after immunotherapy. However, next slide, the overall survival was not here. This is the multi-variant analysis, showing only the history of prior relapse to be significant prognostic factor for event-free survival, but not for overall survival as you will see next slide. There's no difference in overall survival for both groups, meaning patients who were on immunotherapy can relapse again, but they actually don't die. So overall survival is significantly superior than before, higher than 80% for the whole group. Next slide. So what about comparing our results, with those reported by the COG group after using immunotherapy after the stem cell transplant? Can -- do we offer similar results without transplant or inferior? Next slide. So as you can see here, the comparison, which is not truly a comparison, but it just gives you an idea of what we can provide. Post-transplant, 63%, two-year event-free survival reported. Without transplant with naxitamab, we're reporting 74% two-year -- but most importantly, two-year overall survival of 90% first CR patients very similarly to what is reported by the COG post-transplant. Next slide. So basically, what we are now claiming and we are doing to our patients is to provide multimodality management that consists of six months of induction chemotherapy and surgery. And if patients get into complete remission, then they would go on to five cycles of naxitamab plus radiation, total of 12 months treatment, and that's it. So it's mostly simplified, less toxic, less costly, multimodality management treatment. Next slide and final slide. So as a final conclusion of our experience, I can -- that I shared with you, we can conclude that naxitamab and GM-CSF, DANYELZA can be certainly administered to as an outpatient, which improves clearly the quality of life of our patients. Naxitamab and GM-CSF provides also a chance of -- high chance of long-term survival for first CR patients without the need of using stem cell transplant and high-dose chemotherapy. Certainly, this is what we think the right strategy of managing minimal residual disease in these patients and getting them the highest chances of cure. So enhancing the immunotherapeutic responses after naxitamab is clearly one truly way of improving the results that I show you. So we are pursuing now vaccine-type strategies of -- GD2 vaccine-type of strategies to -- in the future to improve even further the results I showed to you. Here is my final slide, and I'm just going to pass over to my colleague and friend Shakeel Modak from Memorial.

Thank you, Jaume. Great presentation. Great work, and you've really built a great program there and kudos to you. So if I can have my slides. All right. Great. So again, thanks again, Jaume. So I'm going to switch gears a little bit and talk about how antibody therapy can be used, in this case, along with chemotherapy for patients with relapsed disease or disease that is refractory, that hasn't responded previously to chemotherapy. And these are the interim results of trials that we've completed, but this analysis is from that interim time point. And the final analysis should be ready by the end of this year. And so we combined naxitamab or humanized 3F8 with irinotecan/temozolomide and GM-CSF or sargramostim, the so-called HITS study, and we conducted a Phase II trial. Next slide, please. These are my disclosures. MSK has institutional interest in this drug. Dr. Chang, who invented the drug also has financial interest, and I'm a consultant for Y-mAbs. Next slide, please. So, as you heard from Jaume that anti-GD2 immunotherapy has improved outcomes in patients with neuroblastoma, but there are still unmet needs in patients, and even with immunotherapy, maybe about 55% of our patients are cured. In addition, immunotherapy alone is not very effective in patients with high burden neuroblastoma, and it's not very effective for patients with chemoresistance soft tissue disease. In a paper that was published in 2017, and then subsequently updated, I think, in 2019 or 2020, the Children's Oncology Group reported about 35% to 40% response rates to dinutuximab, irinotecan/temozolomide in patients with chemo-resistant neuroblastoma. And the initial study talked about 50%, but the combined response rate is lower, about 40% or less. So the question was, can we look at -- because we know that anti-GD2 antibodies have different in-vitro and in-vivo properties. Even before that trial was published, we had launched our Phase II trial with naxitamab, irinotecan/temozolomide and GM-CSF. Next slide, please. So as you can see here, dinutuximab and naxitamab do defer, especially the -- in their binding to the GD2 antigen, which is much higher for 3F8 or naxitamab. And then the other parts of -- other differences are an increased complement dependent mechanism for neuroblastoma cell kill. So it was, I think, a valid question to ask if this antibody will have -- will be as effective or more effective in patients when combined with chemotherapy. So next slide, please. So the difference between the chemoimmunotherapy regimen, which we use, and the COG regimen is that, we divide the antibody into 4 doses given approximately over 10 days, as you can see here in this cartoon. We were able to dose escalate to quite high doses. The total dose per cycle is 9 milligrams per kilogram per cycle. We use a higher dose of temozolomide, and then we do start GM-CSF similar to those patients who received the ANBL1221. The 3F8 here is given during and after chemotherapy. It's an outpatient infusion over 30 to 90 minutes. So these are some of the differences between the 2 chemoimmunotherapy regimens. Next slide, please. For the Phase II trial, the eligibility criteria included measurable or evaluable disease. And in general, we divide these patients into 2 groups because their biology is quite different. First group of patients, we call primary refractory, that means they did not respond to induction chemotherapy and some of them did not respond to induction chemotherapy plus additional chemotherapy. And the other group of patients we term as relapsed or progressive disease that is either they never achieve remission and started having progressive disease or they achieved remission and relapsed. And patients were allowed to have received previous antibody and previous irinotecan and temozolomide. And because this regimen is not very minor suppressive, we accepted patients with a platelet count of 30,000, and we did test the human anti-human antibody response if they have previously received any anti-GD2 antibodies. Next slide, please. Initially, we had just launched a pilot, but we had favorable data, so we converted Prophase II. That Phase II trial has completed accrual, 51 patients were enrolled. And concurrently with this Phase II trial, Jaume has treated about 56 patients in Barcelona, and we are able to combine these data, and we will combine these data when we submit the manuscript. In this slide, again -- slide set, again, is an analysis that was done in 2019. And as I said, I'm hoping to submit the final analysis this year. Next slide, please. So as you all know, DANYELZA received final approval in 2020, and that approval was for osteomedullary disease. But clearly, at least in my view, it has a role to play in other aspects of neuroblastoma treatment. Next slide, please. The mechanistic hypothesis is somewhat counterintuitive, right? So, because if you give chemotherapy, one may expect that effect or sales are going to be -- will lose that function or will be killed by chemotherapy, so somewhat counterintuitive that we see -- we combine chemotherapy with antibody at the same time. However, what we have preliminary data on is that, chemotherapy could actually lead to an inflammatory state which leads to enhanced sector function. And I hope to include all those -- that analysis in the paper, and I'll show you a bit of -- just a glimpse of what we are seeing. And our hypothesis is that chemotherapy releases cytokines and in the presence of this mild inflammatory state the neutrophils, macrophages at NK cells, which are the effective cells for humanized 3F8 are further activated. So next slide, please. So your other patients, at that time, there were 65 patients total. Patients have received 257 cycles. Most patients did not have MYCN-amplified disease, because in the modern era, MYCN-amplified disease, you either have very aggressive disease that is lethal or it is highly curable because it's very chemosensitive. So as expected for relapse and refractory, most of the patients did not have MYCN-amplified disease. To note that many of our patients, and including Jaume's patients, had a large number of relapses. And this is an important point to differentiate between our patient population and that was reported by the COG. Most of our patients had relapsed disease, which is a much more difficult disease to treat. 88% had relapsed disease rather than refractory disease. And at chemoimmunotherapy, all patients had metastatic disease. 65% of patients had previously received irinotecan and temozolomide, 40% had received naxitamab and 32% had received dinutuximab. So heavy prior-treated group of patients, all of them have had several regimens of treatment before they came to this chemoimmunotherapy. Next slide, please. It was very well tolerated treatment. The main -- really, the main side effects were related to naxitamab, which was pain, lab side effects were transient. Neutropenia was seen -- grade 4 was seen in 34%, but only 3 patients had to be admitted for fever and neutropenia, and this was essentially an outpatient treatment in almost all our patients. And so, in general, this is a very well-tolerated treatment which we've done to our patients. Next slide, please. So after 2 cycles, we started seeing responses, which was quite nice to see. The complete -- the major response rate, that means complete and partial response rate, was 34% after even 2 sizes. And we were seeing responses in all body compartments or disease compartments, including 27% in soft tissue, 43% in MIBG uptake, osteomedullary MIBG uptake and 70% in bone marrow. So, unlike antibody plus naxitamab plus GM or dinutuximab plus GM, where there is very little data on responses, but naxitamab and GM-CSF has not been effective against soft tissue disease, whereas the chemoimmunotherapy really is -- it does lead to responses. And as a baseline, if you look at the data, irinotecan and temozolomide responses that are without antibody that's in soft issue is well below 10%. So clearly, this regimen is doing better than antibody plus GM alone or irinotecan and temozolomide alone. Next slide, please. And you can see that these responses are quite robust and very impressive. On the left side in March of 2018, this patient had a huge amount of disease, all the black parts of the MIBG scan represent disease. I would say a QV score of more than 20 and then had a complete response after 2 cycles of chemoimmunotherapy. So very gratifying responses. Next slide, please. And then, if you look at responses in the subgroups, we do see responses both in primary refractory disease and relapsed disease in patients who had previously received humanized 3F8. Those who have previously received dinutuximab and those who had previously received irinotecan and temozolomide. So, this is a regimen in my clinical opinion that can be reused quite legitimately in patients who previously received antibody or those who have previously received second line chemotherapy. Next slide, please. And then, if you look at response rates after 4 cycles, the overall response rate is 39%, which has improved, and some of our patients have continued to responsive. Since this is preliminary data, we have a relatively -- these response rates only mentioned in 56% of patients, and now the final manuscript will have response rates at 4 cycles and at completion of treatment in 107 patients. Next slide, please. Was this response durable? It was indeed durable. So in patients who had an initial response after 2 cycles, they continue to have response after 4 cycles. And they continue to have improving response also after 4 cycles. And those patients would have some response after 2 cycles, had a further response after full cycle. So, that is also an encouraging observation. Next slide, please. Compared to the ANBL, the initial study response rates are somewhat similar. The thing to be pointed out is that, for the ANBL1221 study, only one prior refractory disease or one prior relapse is permitted. Whereas, for us, the median number of relapses prior to coming to treatment was 2. So, it's a much higher risk group of patients who have really received a lot of treatment before and have continued to respond to this treatment. So that is also encouraging. Next slide, please. Sorry, next slide, please. Yes. We have very preliminary data on the mechanistic hypothesis. As you can see, this is in 2 patients, initially at -- on day 1, they start off with -- we measure cytokines in the blood, and day 2 is after receiving 1 cycle of -- just the 1 dose irinotecan and temozolomide before starting antibody. These cytokine levels rose, and one can argue that when antibody is given in a setting where cytokine levels are higher, this will prime the effector cells to enhance the effect of naxitamab. So, although this is very preliminary data, we now have collected, I believe, data on 30 patients. We still need to analyze the data in detail. But encouragingly, this is what we are seeing. And hopefully, we will be able to confirm our hypothesis. Next slide, please. So where do we go from here? The conclusions are that chemotherapy on the HITS protocol achieves major -- chemoimmunotherapy on the HITS protocol achieves major responses in soft issue and osteomedullary disease. We definitely see responses in patients who had received all previous individual components of the HITS chemotherapy and in those who had previously received dinutuximab. Featuring it with administered outpatient was well tolerated, very low incidence of fever and neutropenia, and patients seem to have ongoing durable responses. We and others are considering, and actually already have started combination with other chemotherapy regimens. Children's Oncology Group is looking at incorporating dinutuximab into upfront treatment. But one approach, with Jaume, we are taking is in patients who don't respond to irinotecan and temozolomide with the response to example -- for example, to cyclophosphamide, topotecan and naxitamab or low-dose [ ice naxitamab ]. So, I think, those questions are still being asked, and we don't have those data yet. And so, I think, this is my last slide, and I'll stop here. I think, Steen is going next. He's the Global Head of Transition Medicine at Y-mAbs. So, handing over to him.

Thank you, Shakeel. And my name is Lisby, and I'll shed a light on the pipeline environments and for platform technologies that would end the clinical development soon. Next slide, please. And this is a forward-looking statement. Next slide. So, at Y-mAbs, we have a quite broad pipeline. We have several platform technologies that we work on. We have a bispecific platform called BiClones, where the first compound the GD2-GD3 BiClone already are in clinical development. We do have a 2-step radio immunotherapy platform, which is -- which will be the remaining on our talk. We also work with a vaccine, where we have a vaccine towards GD2-GD3. And also, we have naked antibodies in the pipeline. Next slide. So, the rest of my talk, I will focus on initial data and preclinical information that lead -- will lead to that we move this platform into clinical development in this year. It's called SADA. And the reason for SADA is that we do know that systemic irradiation is associated with significant off-target toxicities. And this limits the amount of possible radiation to 2 in tumor size and hence the [indiscernible]. And the SADA platform is designed to welcome these limitations. The SADA platform was originally developed at strong catering and Y-mAbs has now the license for this platform technology. It represents a 2-step self-assemble and disassembly antibody system, a contract that we refer to as liquid radiation. The idea and the principle is that we can make -- perform a targeted payload delivery with antibody construct and then we can add the payload when it's clear from the systemic circulation. Next slide, please. So it's a 2-step pre-targeted radioimmunotherapy approach, where we at the first step administer high concentration of the protein soft, it's cold. So there's no off-target toxicity. The second step we apply when the free antibody has been washed out of the circulation using in the first case is to radioisotope to a carrier molecule called DOTA, but the platform is very versatile and can allow for different payload dialysis. The perspective idea with the SADA technology is that at a high concentration this molecule form [indiscernible] state, which is optimal for tumor targeting. And then when a concentration has declined, particularly it reduce a sample, and this will result in a short half-life in circulation, which means that we don't need any clearing agent before we add the payload. And the clinical perspective of this is that we aim for a regulatory submission in this year, using GD2 targeting cancers by the GD2-SADA as the first program. Next slide, please. So the target molecule is quite complex. If you look at the upper left corner, it contains of three modules. The first module is anti-tumor, targets a specific tumor molecule derived from an IgG antibody, and where we use [ ST ] binding sections. The second one, the green one, the anti-DOTA is a docking station, again, we use the binding sequences for the DOTA anti-body. And -- DOTA is a key data we use. It's a complexing agent where we bind the radioactive payload to the DOTA and then administer to the patient. And the third compound is SADA, the one to the right, is actually what makes this technology platform unique. This sequence comes from the p53 protein, and it has tetramerization to peptide sequence. And higher concentrations, as you can see in the bottom, it actually forms [indiscernible], so we have a molecule size about 200 kilodalton. And this is very effective binding to tumor science. While the part of the molecule that doesn't bind to the tumor will stay in circulation, the concentration will drop and it particularly will disassemble, as you see on the bottom right corner. Next slide. So in essence, where novel convention radioimmunotherapy or in two-step radioimmunotherapy, you have a quite significant amount of anti-body coupled to circling anti-body, as you see on the left side, where the red depicts the amount of irradiation to off-target or normal tissue, including the bone and bone marrow. On the right, we see the principle of a SADA platform technology, where we first applied the SADA molecule, it binds to the tumor. The half-life in circulation is very short compared to normal IgG. And when we have cleared it from blood circulation, we add the payload of the radioactive isotope. Next slide, please. So in principle, as you see on the left, during the half -- the short half-life, we can actually add one days to two days after the primary administration at the radioactive payload with very little circulating remaining SADA molecules in the patients. And the top bottom, you see similar estimates of a non-regular IgG-based approach. On the right side, you see animal data using PET scan. Here, we have 86 interim DOTA used. And the left of the two pictures you see in IgG-based approach, where a significant irradiation. Outside the tumor on the right, you see a highly specific and selective uptake in the tumor only with minimal or no exposure to normal tissues, 18 hours post administration. Next slide. We have done few distribution studies to release, sustain this very rapid clearance. And if you look at this slide, what comes into eyes is actually the top curve with the blue is the bladder, where we see is rapid it goes to bladder and get cleared, but already a few hours after it's removed from there. And if you look at the femur, which represent the bone marrow or the heart, which represent the bloodstream, you can see a low uptake and a very rapid clearance according to the early preclinical data. And this allows us actually to administrate quite high amount of reductivity due to this very special kinetics. And if we can actually without exceeding the FDA guided maximum organ exposure, for example, the red marrow of [indiscernible], we can administer very high concentration of the DOTA communicated to reach up to [ 18 ], which, of course, we will not do. But it just tells us that this technology here allows for a high exposure to the tumor with much less or minimal exposure to normal tissue. Next. So again, here, our shared data or some of the animal experience. On the right side, we have a dose response, where we can see we're very efficacious, can target the tumor, which is on the right flank of the animal. And it stays intact on the tumor for up to five days, which is the last time point we looked at. On the right, you can see a 24-hour time point, again, a very specific and intense accumulation in the tumor only, which is confirming the very early data. Next slide. And efficacy data, this is published data from 2020 by Dr. Chang, where you can see that both different payloads have efficacy using this platform technology. On the left, we have the [indiscernible] DOTA, which efficacious can eradicate patient-derived xenograft model. On the right side, you can also see, we use another payload, in this case here 225 actinium, so an alpha meter, which really also can eradicate the tumor after only one dose administration. Next slide, please. One thing that's very important for us early on is really to characterize the critical importance of the tetramerization domain. The next slide, please. So we set out to construct a SADA molecule that could not form this tetramer and compare this with a standard SADA molecule that can form tetramers. So in the next slide, I will show two different groups. The first one is the standard SADA molecule, which will go into the clinical development. The second one, we have removed the SADA part of the molecule, so it cannot tetramerize and have a molar 1:1 concentration. And in the large group, we have, again, the monomer, but now at a 4x mono concentration to have the same mass, meaning that we have the same number of binding sites. The next slide, please. And this really confirms the critical importance of the tetramerization domain. On the left, you see very good and clear uptake in tumor using the SADA molecules, on the Group 2, or Group 3 on the right side, we see significant low, almost none uptake if you are using a monomeric construct. So this again, critical importance of the tetramerization domain, is evident by this kind of data here. Next slide, please. So the SADA platform allows a significant target specific uptake and rapid clearance from normal tissue. And the platform technology allows for high dosing of payloads without exceeding the FDA guidance for normal tissue exposure, including for the red marrow. And I think these data, I just presented to you also support the concept of the critical importance of tetramerization domain as part of the SADA molecule. We also, of course, have in-vitro data with binding and also efficacy study that will be published later in a scientific meeting. The SADA complex is to detect tumor target for up to five days after exposure, which is the last time point actually we have explored until now. And for the nonclinical part, we are on track for the IND submission that were planned for late this year. Net slide, please. The GD2-SADA is the forerunner program for this platform technology, and it will go into a large indication in small cell lung cancer sarcomas, but also melanoma. For pediatric development, we are looking for, in particular, neuroblastoma, where it can be positioned after naxitamab therapy. We do have other targets that are quite advanced in the nonclinical pipeline, including B7-H3, it's a humanized B7-H3 molecule. And this can go for both non-small cell lung cancer as well as cancer precision prostate cancer, where we do have proof-of-concept that BW irradiation seems to work, if covered to an anti-body. Furthermore, we have a target GPA33 targeting cancer cells in colorectal cancer. And we also have a target that we are moving toward clinical development, most likely '23 within hematology. And these targets just discussed here are the targets that we do have the lead candidate selected. But we're currently in the lab in New Jersey, in New York, outside York, we're working on more targets within both oncology and hematology. Next slide, please. So this was my last slide. And thank you. I like to hand over to Claus.

Thank you very much, Steen. And I missed that out by saying thank you to everybody that's listening in today. And with that, I'll just give a short overview of all the other programs we have in the company, and let you enjoy what else is on the platform for Y-mAbs. So next slide. So we have basically four pillars that the company is focused around. You just heard about the DANYELZA and the GD2-GD3 vaccine. It's in the pediatric setting for high-risk neuroblastoma and also osteosarcoma. We also had in the setting with this program for at least teenagers and young adults up to age of 30 for the osteosarcoma setting. I'll share a little bit about this today. Our second pillar in the company is our omburtamab platform, where we have the CNS leptomeningeal metastases from neuroblastoma with the iodinated form of omburtamab that is currently very close to a resubmission to the FDA for the BLA. We'll share a little bit about that. And then we have the same product for DIPG in desmoplastic small non-cell tumors. And then we have created the omburtamab-DTPA Lutetium-177, which is in the pediatric setting from medulloblastoma and also being developed in the clinic for B7-H3 in CNS leptomeningeal adult cancers, solid tumors. And then we have the two platform technologies, the Y-BiClone platform with our bispecific antibodies, the GD2 bispecific, and the CD33 bispecific in the pediatric setting for high-risk neuroblastoma and refractory solid tumors in kids and also for pediatric AML. And then we recently started the first GD-2, CD3 bispecific into small cell lung cancer. We'll share it a little bit about that. And then, as Steen just went through the SADA platform that potentially, of course, also will be able to address pediatric settings. But right now, the first is indicated going in the clinic in the adult setting. So next slide. So I'll start out sharing a little bit about the omburtamab and go to the next slide. So since we got the refuse to file in October last year, we have had a total of more than six interactions, discussions and meetings with the FDA to agree on how to analyze data in a manner that would may be satisfactory to the FDA. And we recently here in September had a final, hopefully, Type B meeting. So when we received the minutes from that, we will come out and announce when we expect to have an eventual BLA meeting, but we still expect to have that here in the fourth quarter and get ready for a pre-BLA -- sorry, a BLA filing. In Europe, we have filed for approval, Marketing Authorization Application with EMA in April 2021, and should receive the final set of questions for the initial evaluation by the CPMP and the laboratories here in September. Then we get a clock stop and have three to four months to put together our responses to that. And then hopefully, we can get an approval in Europe by [ the next year ]. Next slide. So this is just reminding you what we showed at our R&D Day in December this year, that to support the data that we created at the MSK Study 03-133, we started the trial 101. And we originally agreed to file with the FDA when we had 12 to 18 patients in that study. As -- and the study was supposed to include a total of 32 patients. All those 32 patients is in the study now, and we have continued enrolling additional patients after that. And -- but one of the key things was would we be able to, in a multi-center setting, to see a survival pattern that is mimicking what was seen at the MSK study. And at least from what we saw initially back in December, that seems to be the case. We are updating all these data and for the resubmission to the FDA, and we have agreed not until now when we are putting together a pre-BLA package, not to do additional analysis, but that will be a part of our resubmission after the BLA. And with that, next slide. So to be able to radiolabel with another isotope than just Iodine-131, we decided to create our omburtamab-DTPA construct. And so that is basically where we put chemically conjugate DTPA chelators on the omburtamab antibody. And that allows for Lutetium-177 to be captured by the DTPA and thereby radiolabel the antibody with Lutetium-177 instead of using Iodine-131. It's a more stable way of radiolabeling an antibody, and it's not nearly radiolabeling as it is to put Iodine-131. Next slide. So for the Lutetium-177 omburtamab-DTPA, we have both a pediatric and an adult strategy. In the pediatric setting, based on our experience from the 03-133 study where we treated a number of pediatric medulloblastoma patients, we decided to say, let's try to have a study in medulloblastoma patients with our Lutetium construct also eventually goes up a little bit versus where we were in total amount of radiation. And then let's also, in parallel, try to address all the adult patients that end up dying from CNS leptomeningeal metastases from a solid tumor and non-small cell lung cancer, breast cancer and ovarian cancer that metastasizes to the brain after they systemically appeared median and survival for these patients even with aggressive therapy induction, radiation, chemotherapy, surgery, median survival is typically around eight months. So we are starting this study now, and both studies are open for enrollment of patients. And we are looking very much forward to see whether we can help additional patients with our omburtamab antibody on the CNS leptomeningeal metastasis setting. Next slide. So just going to chat a little bit about the naxitamab in osteosarcoma. We talked about it at our R&D Day in December also. And since then, we have expanded to two additional sites. The study was originally designed to recruit 39 patients. These patients are patients that have been put into remission in frontline, then they relapse. And when they relapse, they typically have a solitary metastasis either in a lung or at the epidermoid bone side, then they all undergo surgery. And typically, they would be in complete remission after that. Now a lot of studies have been tried to prevent these patients from relapsing a second time. But nevertheless, 85% of the patient would typically relapse again already within the first 12 months, meaning that they have microscopic disease that are just not visible after the surgery. So the idea here is that we give GD2 antibody with GM-CSF to prevent these micrometastasis from starting to grow and eradicate them with a naxitamab antibody or DANYELZA antibody. Next slide. So the study has now recruited 39 patients. Seven of the patients were extra pulmonary disease patients, and we want to have 39 with pulmonary only patients. So when we get to those 46 patients, we can do the final analysis. And we expect that to be possible by the end of this year, early next year. And then the idea would be to share those data and also the design of a randomized study that we are planning now in these second-line osteosarcoma patients and, of course, get a publication of the data as quickly as possible. Next slide. So let me chat a little bit about our Y-BiClone platform since Steen have now given a nice presentation of the SADA bispecific platform that targets DOTA and tumor targets. Our Y-BiClone platform is a more traditional bispecific antibody platform where we activate T cells with a CD3 binder and with one part of the antibody and address binding to the tumors with the other part of the antibody. Let's go to the next slide. So we have our first bispecific, a GD2-GD3 bispecific antibody called nivatrotamab. There's two clinical studies ongoing with this construct, an adult study in small cell lung cancer and a pediatric study, including neuroblastoma and osteosarcoma patients. Now these bispecific antibodies that we are working on is different from what most other people are using. Normally, you just replace one of the fab parts of the antibody with a CD3 binder and the other is continuing to bind to the tumor. We have maintained the two tumor binding parts of the antibody. And then instead, added a single-chain Fvs, at the end of the light chain of the fab, that has a low affinity CD3 binder. And we tested out this construct versus both traditional BiTEs, which is just two single-chain Fvs that are bound together and traditional heterodimeric IgG constructs. And you can see this is a logarithmic curve, but it looks like the BiClone is at least three to four logs better in a specific license induction antitumor effect than the heterodimer. So the BiClone construct, we are very -- seems to be extremely potent compared to classic bispecific antibodies. And we go to the next slide. So in the small cell lung cancer setting, where we're going in, we have quite good documentation that a broad spectrum of these express GD2. And most of the lung cancer is about 13% to 15% of all the lung cancers and are very distinctly different from non-small cell lung cancers. And there's very, very poor survival probability for the patients in this setting. Unfortunately, most of the patients is having both distant or local regional spread of the disease when they are diagnosed. And that means that all stages combined has a five-year survival rate of approximately 6%. So these patients progress very quickly. Typically, you see a very quick response to chemotherapy. Even if you radiate small cell lung cancer cells, they also respond, but they all can't resist this very quickly and develops resistance, and then they just keep progressing. So there's definitely a significant unmet medical need here. And since it's very good expresser of GD2, we found it was a great adult indication for our bispecific antibody against GD2. So next slide. So we are -- versus the administration form we used in the first study in collaboration with MSK, where we gave intravenous administration of the bispecific nivatrotamab antibody, we decided, based on what we saw there, to try to go for a subcutaneous administration that now seems to be known to reduce cytokine release syndrome and give them a marked slower onboarding of the antibody with a Cmax estimated to appear two to five days after the subcu injection of the antibody. And then we also changed dose frequency. So based on discussions with KOL and patient feasibility and what we hope would be a more optimal way to go with this. So in cycle one, we dosed the patient on day one, day eight and day 15 as kind of like induction treatment. And then we go to biweekly treatment up to half a year. And after that, if the patients are still in stable decision -- situation or remission, we offer to continue on a monthly basis. And then we, of course, use our premedication with methyl prednisolone and dexamethasone. Next slide. So we have seven sites that are to be involved in this study, and three sites have been activated and have started screening patients. We dosed the first patient in August 2021, and the patient is still under study. And then with that slide, let's move on. So the second bispecific construct we created is the Y-BiClone construct, a CD33/CD3 for pediatric AML patients. So Study 801, we just filed the IND to the FDA in June. And after hopefully clearing the questions we have received from the FDA, we expect to be ready to start enrolling patients in the first quarter of next year. This is a collaboration with [ PedAL and COG ], and we have received interest from more than 10 sites to participate in this study. So we're very excited about this and looking very much forward with our second Y-BiClone construct into patients early next year. Next slide. And let me finalize this short summary presentation with our financial summary. Next slide. So at the end of second quarter, the company had more than $230 million in cash or cash equivalents. And since we started the company, we have raised $489 million. We had a PRV that sold for $105 million, and we netted $62 million of this based on our original splitting agreement with Memorial Sloan Kettering for how we would handle income from PRVs received from the products that we have licensed in from MSK. We believe, and also based on what most analysts guestimate, that we will burn probably. So we end the year with between 170 and $180 million in the bank. And we are very satisfied with our current situation. So with that, thank you very much for listening to this part of the presentation, and we should be able to move on to questions. Thank you.

Thank you, Claus. [Operator Instructions] So the first question comes from Tess Romero at JPMorgan.

Yes, can you hear me?

Sure.

On the osteosarcoma strategy, I think you noted that in addition to Phase 2 Study 15-096 you will be running another study in osteosarcoma. Can you maybe explain that rationale for running another study? And then I had one more for the KOLS.

Well, we still don't know what requirements that will be made for a regulatory filing and it may very well be that there may be a need for a randomized study. So we -- rather than waiting until we see the final analysis and have a feedback from the FDA to start prepping for it, I mean, then we start working on getting more clinical experience in the osteosarcoma setting already now. So we still need to have some more regulatory feedback before we know how we would design an eventual randomized study in the second line osteosarcoma setting or whether we should move it up to an earlier stage when we have seen the data from this study that is ongoing.

Okay. Okay. Got it. And then my other question is perhaps for Dr. Mora or Dr. Modak. When we are thinking about kind of the current standard of care in front-line, high-risk neuroblastoma, are there any [ differences ] that we should be thinking about in terms of how patients are managed between the U.S. and Europe? Any differences you would note on that?

Yes. Sorry, I missed the point. The audio wasn't that clear. You're asking the differences between the European and American standards for newly-diagnosed patients?

Yes, exactly. Any differences we should be thinking about and how patients are managed?

Well, certainly, induction chemotherapy is fairly well standardized nowadays. There are some differences, but everybody agrees upon the importance of induction chemotherapy and surgery. So this is fairly standard nowadays. Some -- and rescue regimen for those patients who don't respond completely, however, there are different strategies now being tested, including adding the antibodies upfront together with chemotherapy. So those are strategies that are now currently being tested both -- in both sides of the Atlantic now. Other than that, I think for patients who get into complete remission, I think now we should make all the efforts possible to question the high-dose chemotherapy strategy and move on to more broadly available and more easily and broader use of antibodies earlier for the consolidation of these patients. So that would be my suggestion here now.

The next question comes from Avatar Jones at Morgan Stanley.

My question has actually been answered. So thank you for that.

The next question will come from Alec Stranahan at Bank of America.

So good to see the frontline data for DANYELZA. But I guess, Claus, how big a factor it is the data support of no need for stem cell transplant in terms of your ultimate go-to-market strategy in the frontline? Do you see this as the major differentiator versus current treatments? Or are there other factors, maybe event-free survival or the safety profile that you'd also point to? And then I've got a follow-up for Dr. Mora.

Well, I think the need for a lack of same bone marrow transplant in the frontline setting really doesn't affect the need for the -- for immunotherapy with the GD2 antibody. I think Dr. Mora is making a pretty clear case. And together with the data that has been published from also MSK, that there's no benefit to the patients of these bone marrow transplants. But that does not affect the need for a GD2 immunotherapy. So the bone marrow transplant apparently doesn't clear the patients from -- and prevent them from relapsing. If you see the old data, it's pretty clear after the bone transplantation frontline patient had received all standard of care. Without immunotherapy, you have a two-year event-free survival in the ballpark of 42% to 44%. And adding an immunotherapy on the top of that, as dinutuximab adds another 20%. So the bone marrow transplant doesn't clear the patient. So there's -- and the survival data speaks for themselves, the overall survival data. So -- but I don't think it affects the uptake of DANYELZA. The data on DANYELZA in frontline is very strong, as Dr. Mora has presented and published in his paper, two-year event-free survival of 74%. I mean -- and that seems also, as he presented this summer, to be holding up to three years, so -- which is clearly in excess of what has been published for dinutuximab. So I don't think that's affecting it. So that was a long answer to a short question.

Okay. Great. And then maybe just one for Dr. Mora. Could you talk about the potential issues with current cytokine use, such as IL-2 as a component of maintenance therapy currently? And maybe along that point, what differentiates DANYELZA from, say, Unituxin in terms of quality of life?

Well, I'm going to answer very quickly, easily the issue of interleukin 2. I think the SIOPEN Group, the European group has clearly shown that in a randomized study actually that interleukin 2 is not only -- not adding benefit, but actually it's counteracting. So, interleukin 2 has disappeared now from the cytokine profile of drugs to be administered in this setting. I know it is still in the labeling indication of -- in the U.S., but certainly not in the European group is no longer used.

COG guidelines were released last year to not use it to COG members. So it's not being used in the U.S. at all.

So this is gone. Right. Thanks, Shakeel.

The next question comes from Joseph Thome at Cowen.

Maybe one for each physician. First, maybe Dr. Mora, the overall safe tolerability profile of DANYELZA looks great, but there were a few patients that did have to discontinue. Can you just discuss a little bit the overall rate of, I guess, dose interruptions or dose reductions that you've seen necessary with treatment, maybe specifically to address some of those blood-level changes that we're seeing? And then second question, maybe for Dr. Modak. In the patients that are -- that do have an initial CR to therapy that then relapsed that are then treated with DANYELZA, does the duration of initial complete response after induction therapy matter to patients that have a long initial CR, see better responses to DANYELZA or vice versa?

I'm going to address first question. First part is that we don't reduce dosing. So either patient sustains the full dose and full cycles as planned or is it released from the protocol. As I said, there were four -- five patients, actually, out of the 73, which is almost 7% of patients who had a grade 4 toxicity in our experience and had to be excluded from the treatment. But there's no reducing dosing for managing toxicities. I have to say now, though, that we have come up with better and safer ways of providing the drug that we are working very hard. And so in order to reduce these intense reactions, I am certainly hoping -- and actually our current dropout rates have dropped significantly below 4%. So I think the more we learn and the better we learn to administer naxitamab, I think the dose reactions can be managed safer and less and less patients will drop off from trial.

Yes. I think just to second that point is that these reactions are more like infusion reactions seen with various other monoclonals as well, might be slightly higher rate than say rituximab, but these are infusion reaction, essentially allergic responses, which lead to patients coming off. Now in terms of the second question, I think there is a group of early relapsers within the MYCN amplified group who really can't be sandwiched with any treatment. But if you exclude those, I don't think -- and I haven't looked at it statistically, but I don't think there's a difference in response rate. When the patient relapses, one kind of observation supporting this is that we do see -- we do have quite a high response rates even in patients with second relapse. So my impression is that if they're going to respond, they're going to respond. And what we see is that patients who respond after two cycles will continue to respond. Patients who show no response after the second cycle are unlikely to respond.

The next question comes from Arlinda Lee at Canaccord.

I was curious about -- from Dr. Mora, you talked about the proportion of patients that could not complete treatment. And I was curious if you could help characterize that in the context of your real-world patient population? And then for the company, your SADA and BiClone platforms, there's a lot of targets that you can explore. So I'm curious about your appetite for collaboration and potential outlicense or how do you think about how your internal and potentially external pipelines might evolve and over what time frame?

Well, thanks. Regarding your first question, if I understood well, I highlighted there were 16 patients who could not complete the treatment out of the 73. Six -- so actually five, as I said, for grade 4 toxicity, one because developed high levels of blocking antibodies. So patient could not pursue on the planned treatment, and 10 because patients actually relapse on treatment. So I did not get the -- what you meant about the real-world question. So basically, it's, as I said, 7% of toxicity rate, but the rest was because of earlier relapses.

I would say, similar to dinutuximab. I don't think it's markedly different.

Thank you. And Arlinda, to your question about partnering on our bispecific platform, we are definitely in discussions with a number of companies and potential partnerships, both for our bispecific, but also for SADA platform. There's no doubt that there is quite a bit of interest in particular in our SADA platform, and everybody is waiting to see whether this connection can be put into patients, which we are working hard. And as we are striving, as Steen also said to get our first IND into the FDA before the end of this year, and then with a little dialogue forwards and backwards, hopefully, before summer next year, we should be ready to start enrolling the first patient on the first SADA construct. And I think that would trigger even further interest in the tech platform. As you said, there's an unlimited number of targets that you can work on, and it would be our clear expectation that we should be able to close at least one partnership for these two platforms before next summer. Was that what you were asking?

Yes. Thank you very much.

So the last questions will come from Sebastiaan van der Schoot at Kempen. We can't hear you. I think we lost Sebastiaan here. So I'll turn the call back to Claus for closing remarks.

Well, let me just close off by, in particular, thanking Dr. Mora and Dr. Shakeel for participating today. And also, thanks to everybody for taking time to listen to our presentations today. And with that, enjoy the rest of your day. Thank you very much.