Welcome everybody to the 2022 Y-mAbs R&D Day. We will have presentations by management over the next hour and a half, and we're very excited to hear their plans. Please note the disclaimer here and the forward-looking statements, and you can read them and check the website and the SEC filings. At this point, I'd like to invite Thomas Gad, Founder, Interim CEO, Head of Business Development and Strategy, and overall inspirational guy to come up and do the slides. Thanks. Sure. Thanks. Good morning, everyone, and thank you for being here today and spending time with Y-mAbs. We are in an exciting period of time, a little bit overshadowed by our ODAC vote, but we will manage through that as well. I'll start with a short update, company update. We'll hear from Steen Lisby, our Chief Scientific Officer, who will focus on our exciting SADA development. After that, we will hear from Vignesh, our Chief Medical Officer, who will focus on mainly DANYELZA. Just to address omburtamab, which I think it was obviously a big disappointment for the company. After having the ODAC meeting October 28th, I don't think anyone was surprised to receiving a CRL letter. The next steps that the company is doing is we are, as we speak, preparing a response book for a Type A meeting. We plan to submit that in next week or end this week, actually, in order to have a turnaround time of 30 days. We will have a Type A meeting mid-late January. I think, you know, we will explore what else can be done. I think the company is in a position where we have done everything you can do in this indication, but we will update everyone about the outcome of that Type A meeting and what will happen with the omburtamab program after that meeting. Unfortunately, we can't share any more insights on omburtamab at this point in time. you know, Y-mAbs is, we're refining our focus, and we are continuing to develop the DANYELZA franchise. We have a single center study at MSKCC that is fully recruited, which we are waiting for that study to read out in front-line high-risk neuroblastoma. We also have a second line, recurrent pulmonary disease only osteosarcoma trial that is almost fully recruited at MSKCC. We are also anticipating that eventually to read out, as a second indication, from neuroblastoma. We have this year, as you saw, we got an approval in China. We got an approval in Israel with Takeda, and we filed a BLA in Brazil with Adium, or also Tecnofarma. I think we are really looking at expanding DANYELZA's international footprint quite nicely. We got a $15 million milestone trigger at the China approval. They have a dedicated sales team of 15 people, and we're going into 40-plus hospitals next year. We're very excited about that launch as well. We have made tremendous advancements on our SADA tech platform that we licensed in only in April 2020. It is obviously a completely novel radiopharmaceutical tech platform. It's highly differentiated to any other radiopharmaceuticals out there at this point in time. We are very excited, to give you an update today on that platform as well. Finally, we had $115 million in cash on hand at our Q3. I think it's important to mention that omburtamab revenues and PRV was never part of the company's guidance. I understand when we didn't get an approval, we lost the opportunity for monetization of a PRV, which would have brought in non-dilutive capital around maybe $60 million to the company. You know, our task is to turn around, make it an opportunity, and manage through that. I think we are comfortable being conservative and extending our cash runway into 2025, but we'll come back to that a bit later. Just to quickly refresh ourselves about the opportunity of DANYELZA that has been. It was approved in November 2021. No, November 2020, launched in February 2021, and today, we guided $45 million-$50 million US national sales. I think we are quite excited about. We kind of relaunched the product in 2022. Sue Smith, who was hired in January, implemented a fair amount of new strategies, and I think we're seeing them translating into more prescribers. This is a slide to show you what we really can do with the product. Just to address the adult indications, we will address those through ISS. We will not spend budget on these indications ourselves. We will do it through ISS's proof of concept, and then that should lead to partnerships. We are not throwing budget at these larger indications. We are going for neuroblastoma second line. We are hoping, we are waiting to see how the frontline MSK study reads out and the osteosarcoma second line study at MSK reads out. We're well on the way with our ex U.S. sales, expanding that footprint, and then we are looking at ISS's to create proof of concept for the large indications. This slide, I guess something happened to it. Just an update on what really Q3 I think was quite an important quarter for DANYELZA. I mean, those... You know, we are heavily focused on some key accounts, and we have identified 63 key accounts, and they stand for more than 75% of the overall GD2 market. That's what we're addressing. We are seeing some very nice trends out of the Q3. We are seeing sites that are treating two or more patients growing outside of MSK. Seven out of the 11 new patients were started at large academic centers. That's a very nice trend as well. The percentage of patients actually receiving five cycles or more is also increasing, so that tells you we are coming more down towards our label instead of being used in 3rd line. You obviously don't want your drug to be used in 3rd line because you have efficacy dilution and less duration of cycles. A very good trend. I think it was the first time we actually took market share, which we used to expand the market, and this time we actually took 12% of the overall GD2 market in the U.S. That's a very positive trend as well. I just spoke about China, but I just had another bullet on it here. We are very excited about that launch next year. We haven't disclosed economics of that partnership, but it's a very healthy partnership and pricing is healthy and it's a significant opportunity for the company. SADA. SADA, we have invested a significant amount of money into CMC and de-risk that platform over the last two years. We've shown some very nice data where we can target tumors with high payload exposures without exceeding acceptable normal tissue uptake. I think the AACR poster was very nice, where we showed that why we need a tetramer versus a monomer. Let Steen talk more about that, but it just was very superior in all the different areas you look at tumor uptake, avidity, time on target, and the antitumor response is seen in the animal models. Very exciting. You know, the SADA platform is the nice thing about that, it's, it's potentially we can de-risk that platform very early on because of imaging data. I'll let Steen talk more about that, but it's, it's, you know, these programs, you infuse the protein, you infuse an imaging dose, you see if the protein lights up, and then only then you move the patient over to a therapeutic dose. Early on, you can de-risk your programs and, and validate the mechanism of action. First site, I'm already behind here. First site was open. I think actually the second site was open. We are running fast. We are planning a total of four to six sites in Q1, and then we're adding more sites later this year. What we wanna do with the platform is third-party target optimization, failed phase III assets, and then also looking at our large indication assets to license those out and keep the pediatric indications for ourselves to build up a rare pediatric disease portfolio. That's the overall strategy with SADA. You know, depending on what happens with the FDA, I think the company, you know, we are very well-focused, and we know exactly where to focus and throw budget. This is just a summary of what happened this year. I can't really tell you what more is gonna happen until we have more clarity from the FDA about omburtamab. You know, omburtamab was really the priority review voucher initially. Monetization of that, and that is obviously not happening anytime soon. We'll see what happens with these programs and if we get a clear pathway with the FDA, and if not, we'll manage that as well. If we look at the company and what is Y-mAbs, you know, I've tried to kind of make this focus of what will generate value, where will the revenue come from, and, you know, eventually, you know, SADA will or should overtake everything in terms of partnerships, revenue, and royalties. Initially, we are working down in this circle. We're adding our ex U.S. partners. We are looking at ISS's to see if we can get proof of concept to move DANYELZA into large indications, but that would be a completely new dose studies because you would need to dose it differently than you do it today. You need to dose day one or day eight or day one or day 16. We'll do that with partners instead of spending money on that, and then we get into SADA. That's where we are today. And overall, you know, omburtamab have overshadowed a little bit of what's going on in the company, but I think we're comfortable in moving this forward and excited about doing it. With that, I'll give the word to Steen. Thank you. Thank you, Thomas. My name is Steen Lisby. I'm the Chief Scientific Officer here at Y-mAbs. Today I will share you with you where we are with our pipeline, in particular with the SADA programs. Today also I will reveal the second SADA program that we've been working with and we are going public with today. It's very important to understand why SADA is unique, and I think I've to go one step back and repeat something that was actually discussed a year ago. It's very important for you to understand this is a unique platform. The aim with the SADA is to develop what you call a two-step radioimmunotherapy platform. Also to develop a platform that could be used for targets, more targets, as well as more payloads. It's very important for us to have a platform that differentiate from what's out there. Due to the molecular structure, we have the probability for this molecule to disassemble and also allow for a PK optimization that allows for a subsequent payload. This is ideal for a two-step procedure. What we've seen so far is that in the non-clinical research, most SADA protein actually can be removed from the circulation in normal tissue before we come with the radioactive payload. This results in a much less normal tissue exposure and better safety profile in non-clinical assays. This is really a benefit risk. It's an upside for the SADA that you don't have the payload circulating attached to a protein. What we've seen so far is a very high tumor to tissue ratio, both for compared to blood, but also tissues, including the bone marrow. The two-step approach potentially will allow also the protein administration to be separated from the handling of the radioactive payload, which is good not only for the research setting, but also later for potential commercial setting. This is how the molecule looks like. It consists of three segments. The first segment is a tumor targeting segment. It's derived from a normal IgG-based antibody, where we take the Fc regions parts of it and linked it to a DOTA binding sequences. Why are you using DOTA binding sequences? This is because we use DOTA as a chelator for the payload. This means that when we come with a payload later on, the only place the payload can bind into humans, that is actually on this segment here of the SADA molecule. It means that either it binds to the SADA molecule or it will be removed from the circulation immediately. Lastly, the third part is unique for the SADA. It's a SADA molecule part. It is a domain from the TP53 molecule that has what we call a tetramerization peptide. This means that at higher concentrations, it will actually form a tetrameric structure around 260 kDa. At lower concentrations, it will automatically and predictably disassemble. All this we have discussed before, that is the basis for this platform. The first step is a cold step, meaning that when we give the protein, it is in a circulation, there's no radioactive payload attached. First, after the binding and removal of the protein from the circulation, we add the hot radioactive payload, and this, according to our non-clinical data, will give much less non-specific binding. This is how it looks like in animal models. We've shown this before also, and it'll be published in 2020. Let me see here. If we compare with a normal IgG-based antibody with a six-eight days half-life with a PK optimized SADA protein with a roughly 8-10 hours half-life, you can see that if when we come with the administration of secondary payload, like 48 hours after, the vast majority is removed from circulation. Here on the left, we see a two-step procedure with the IgG-based approach. The IgG circulates longer. It's not cleared when we add the payload. You see huge unspecific binding. Here to the right, you see what happens if you use a two-step SADA approach. All the circulating non-bound SADA has been cleared from the circulation when we come with radioactive payload, and we have a very specific and intense uptake in the tumor only. This is why we are so excited by this platform, and this is why we are moving this towards clinic very soon. What we have been able to do at Y-mAbs, even though we are a small company, is to have a really good interaction between our CMC group and our non-clinical development, so we very early on can get material and start the non-clinical development. This means that even though we don't even have the master cell bank established at this time point, we can start assay development, we can start pharmacology, we can start the toxicity programs. This allows Y-mAbs actually from a lead to have a regulatory submission packet that we can do this within two years. I think this is a huge advantage for us that we can turn around new molecules at speed when you have the lead candidate selected. This is what we've been working with the last two and a half years, as Thomas Gad was alluding to. We got the license from MSK in April 2020. We have early on looked for several targets in the early assessment, here today, I will present you the second SADA molecule that are going into clinic hopefully end next year. This is a CD38-targeting SADA molecule. The first SADA molecule we developed was a GD2 SADA. That's been non-clinical presentation, as Thomas was alluding to, we also presented here at ASR earlier this year, where we really showed the importance of the tethered bispecific as compared to only a bivalent monomeric version. We have the lead candidate selected. We have submitted a full IND package that has been approved by the FDA, we have an open IND. I'll come back to where we are with the clinical sites just after this slide share. The second SADA actually is a fast follower. We have been working with this now for more than almost two years from now. We have the lead candidate selected. We are in the process of finalizing IND regulatory submission package with a goal that we can have the data ready for Q1 next year and submission H1 of next year. On top of that, we work on other molecules in the early assessment, including the B7H3 SADA, but also targets like GPA33, which is a colorectal cancer target, and HER2, of course, breast cancer and gastric cancer targets we are looking actively at the early part of the development. GD2-SADA, the first SADA that Y-mAbs has produced and the first SADA that is entering clinic, the first study is called Trial 1001, and it's open for enrollment. What is GD2? We have talked about it before also with DANYELZA. It's a sugar molecule. It's a carbohydrate antigen. It's a valid target that have been approved by the FDA for RGD-based antibodies. We know that there's limited tissue expression by GD2, but there is expression of peripheral neurons and also on pain fibers, and we are looking into that as a part of the early development. Also we try to see whether we bind, and luckily enough we see very little binding with the GD2 SADA to those structures. We know this molecule is highly expressed in neuroendocrine tumors, including neuroblastoma, but also in sarcomas, melanoma, and small cell lung cancer. In adult indications that are the target for the first clinical trials with SADA according to the FDA guidelines. The development we start with of course will be in the relapsed refractory setting in a phase I controlled setting. The status is that we have a fully developed CMC package, an approved IND, CMC package. We have also fully FDA non-clinical IND package and have had a discussion with FDA for approval of our first human phase I protocol. Here again, first site is open yesterday. Actually site number two was open, and the trial is listed on clinicaltrials.gov. This is just a few data here showing the non-clinical efficacy, not only in neuroblastoma patient-derived xenograft models, but also in small cell lung cancer data. This is what it looks like in time course. This is a biodistribution study we did with tumor-bearing mice. What we see very early on is that there is a few hours after it, still something in the liver. We can see the sparsely around in the body. We have a quite high intensity in the tumor, and in this case here also in the bladder. We can see very quickly already 24 hours after and 48 hours and even five days after, we have specific and only uptake in the tumor. It stays on up to five days, which was the longest time when we supported the study. It meaning that the normal tissue exposure, even though of course there will be a normal tissue exposure as we inject it in the bloodstream, it's very brief. We also seen that on the biodistribution studies here. This is a non-tumor-bearing animals. This is murine models we are using here. We see an initial spike in the bladder. This is expected. This is the way you excrete your radioactive payload, and then very rapidly clear from the bladder. Also very importantly, when we look for other organs, including the liver, because many proteins goes to the liver of degradation, it doesn't matter with a two-step procedure because the protein goes there internalizing the liver cells. When we come to the radioactive payload, it cannot bind anymore because it's not on the surface. Also, if you look for the femur, which represent the red marrow, and the heart that represent the bloodstream, there's very little exposure here, meaning that the unwanted, non-target specific binding is very low with this structure here. We can actually, by doing... by looking at this data, dose very high at the tumor. This means that if we look for both red marrow, kidney, and liver as three of the major organs for antibodies we want to look for, we can easily with a study design we've done now, dose up high, maybe even up to 1 curie if we need to do that, without exceeding even 5% of the organ toxicity limits, meaning that there's a very large window between what we administer to the patients and the safety tolerability for the normal tissues in the patients. There are, of course, many questions we want to address in such a first in human clinical trial. What we have discussed with FDA and agreed with FDA is that we have a three-step procedures in the phase I, exposing roughly 60 patients. In the first part of the study, we will expose the protein dose escalation, but also importantly the distance in humans between the SADA protein and the payload to be delivered. Because we know very well what happens in a non-clinical setting. This is the first time ever with those humans. As Thomas was alluding to, we have a theranostic approach. Meaning that we give an imaging dose of the radioactive payload first, and we use 177 lutetium DOTA. The good part with 177 lutetium is that you can visualize it by SPECT/CT scanning. Before we dose higher in these patients, we actually have an imaging performed on the patient. In patients where we can see tumor uptake, we are allowed already on the very first patient to give 200 millicurie of therapeutic dose to the patients. It means that we quite quickly can dose escalate and potentially see a positive outcome in the patients. Please remember, this is a phase I study that we are allowed to do this in. In the second part, we dose escalate from the starting radioactive payload up, and keeping both the protein amount of protein and the spacing intact from defined here in part one. This we use in part two, what you call part B, where we dose escalate on the radioactive payload. Also actually, we were allowed to have repeated dosing as what we call a part C, where we can see long-term safety as well as outcome. All of this we can achieve in the very first clinical trial. Where are we with this trial? We plan, as Thomas was alluding to have a limited number of trials open because this is a phase I scenario. We plan actually to have six to eight clinical trial activated here in the U.S. two of them already now are open, is HonorHealth and also City of Hope in California. Both of them are now active and starting to screen for patients. For now we have at least two patients lined up that we are looking for, and hopefully we will include those patients early next year. If we're very lucky, we can have the first one included before Christmas. That's to be hopeful. We have the study lead. It's the University of Pittsburgh, Dr. Taofeek Owonikoko, who's a lung cancer specialist. Also we have specialists within sarcoma field as well as melanoma field. This leads me to the next SADA because the GD2-SADA is addressing solid tumor platform. We also want to explore the SADA in hematological indications, so in liquid tumors. To do that, we have developed what we call a new SADA for liquid tumors called CD38-SADA. CD38 is a well-characterized membrane associated target. It's again, a valid target. We have monoclonal antibodies developed and approved by the FDA for that target. What we do know about the target is that it's highly expressed in major lymphoma indications, both B and T cell origin. It's also in plasmacytomas as well as myeloma. We do know this target is can internalize, and this of course, has been part of the selection or deselection early on in the non-clinical development to have the lead candidate selected. This is potential a new way of addressing CD38 positive tumors. It's addition to the toolbox for the physicians, in particular for the relapsed refractory setting. What we do know also from other antibodies is that CD38 antibodies normally do not cross-react to standard animal species. In order for us to build our non-clinical package, we actually accessed a commercially available CD38 human transgenic mouse. This we obtained from a commercial breeder. What we have done is that we have validated this mouse model. We have validated it so we know that the expression both on peripheral blood cells as well as tissue, there was sufficient overlap between what we saw in our model and what we know from the humans. Based on both the normal phenotype and all the relevant tissue binding assays we did perform, this model was considered to be suitable model for assessing both PK toxicity as well as biodistribution for us to go into clinical development in humans. Where are we with this second SADA molecule? We are aiming to finalize the whole non-clinical package early next year, so Q1 next year, with submission of a full regulatory package to the FDA in the H1. This is the intent, we are getting the very last data in now. If they are not disappointing us, I think this is a timeline that we are striving to reach. The protocol, which in future will be called the TWILIGHT 1 clinical protocol, is a basket trial. It will assess safety and also outcome in adult patients in hematological indications known to express the CD38. This would be a standalone protocol to establish proof of concept in these indications and can be followed then within each indications that we've seen positive signals from. This is just some of the data that we've done so far. What we see here is very limited uptake in normal tissues. We will expect in the urine bladder because this is the way you excrete it. Again, as we've seen here, as we saw for the GD2-SADA, we have an initial uptake in the bladder, but very quickly this exposure is disappearing. Also, this is a non-voiding tumor setting, so some of the animals even had it in the bladder fluid. Also, we see minor signals only in the kidneys, but again, this is a route where you excrete protein, so this is expected. Else there's no major uptake, and this is very positive, not even in the liver and not in the red marrow, which we can see here. Very little uptake in those organs that we think would be the critical organ and dose limiting. We have done tumor models. We know that it binds a lot of different tumor cell lines, both here in the Burkitt's lymphoma cells, but also mantle lymphoma cells. We have seen dose responses in some of our tumor models here. This is a Burkitt lymphoma model, xenograft model, where you can see we can eradicate tumor in the highest doses with only two exposures. To summarize our SADA program, we now have one SADA program in the clinical with an open ID. The project is open and the first patient expected to be included, hopefully just before Christmas or at latest Q1 next year. The second SADA program, we are almost finalizing the non-clinical development. We are on track for a Q4 or a Q1 2023 regulatory submission to be submitted, and the idea is currently scheduled to be submitted the H1 next year. On top of this, we're also looking for the framework. Can we optimize it further? We are also looking for, can we put other payloads on top of lutetium? There's a lot of work ongoing for alpha emitters, and this is... I mean, we're not the only one looking for alpha emitters as well. We do have a special linker called PROTEUS-1 that is designed better to capture alpha emitters as compared to beta emitters. We are looking for yttrium as a beta emitter, so we can use it both for imaging as well as for therapeutic purposes. I think that was the status for the SADA program. Thank you. I hand over to Vignesh to talk about the clinical DANYELZA. Thank you, Steen. Good morning, everyone. It's great to see you all. I'm Vignesh Rajah. I'm Chief Medical Officer. It's a real pleasure to be here today, to share with you some key updates on specific programs relating to DANYELZA. This will be a slight change of tack from what Steen's presentation focusing on early-stage development. There's a couple of programs that I'd like to share with you today. Firstly is our pivotal randomized control trial in osteosarcoma, which we are very excited about, and I'll share with you a few more slides around the design and the status of this study. The second study you can see here is an investigator-led study looking at the use of DANYELZA as part of induction treatment. This is frontline use of DANYELZA in high-risk neuroblastoma patients. you've seen this kind of slide before. This is just as a background. As you're aware, DANYELZA is a humanized monoclonal antibody targeting the GD2 antigen. you know, although this GD2 antigen has limited expression in normal tissues, we know it's overexpressed in a number of cancers as listed here, and this was the rationale for development and ultimately approval of DANYELZA in high risk, relapsed refractory neuroblastoma. equally, as you can see, there's high degree of expression in other cancers of interest, notably here osteosarcoma, which we are gonna push on, and we are about to start our randomized phase III trial, which will hopefully lead to regulatory approval. The other studies in the adult indications, as Thomas alluded to earlier, our strategy right now is to support investigator-sponsored requests for now, really, if we wanna stimulate a clinical development program, we'll be hopefully looking for partners to collaborate with us in these indications. This includes indications such as soft tissue sarcoma, triple-negative breast cancer, as well as melanoma. Why investigate? Why are we interested in osteosarcoma, apart from the fact that it is highly expressing GD2 antigen? We all know it's an area of high unmet need, and as the slide shows here, roughly about 1,000 patients are diagnosed with osteosarcoma each year in the US alone, and similar numbers in Europe and in China. For over two or three decades now, there's really been nothing that's made any inroads in terms of improving survival in this tumor beyond chemotherapy. It's still very much the mainstay of treatment now, which is combination chemotherapy, which is shown to be superior in terms of survival compared to surgery alone. This is pretty much the closest we'll get to standard treatment. Although many institutions, both in the U.S. and Europe, there isn't a natural consensus which combination of chemo is used, but there are some official NCCN guidelines and ESMO guidelines which do highlight the recommended chemotherapy treatments. Of course, chemotherapy is not a cure. Most of these patients will relapse due to micrometastatic disease, and as you can see on the slide here, the survival is pretty poor. I mean, the prognosis is dire in these patients, and this is what's tragic about this tumor. Despite several promising agents coming into development from all sorts of places, nothing's really made much of an impact. There's a huge unmet need for us to look into this indication. This is a kind of a guideline published in the NCCN guidelines and ESMO guidelines, recommended treatment pathways for treatment of osteosarcoma. Generally, most centers will use a combination of what's called a MAP regimen, which is a combination of methotrexate, doxorubicin, and cisplatin or carboplatin as first-line treatment. This is after surgery. Some of these patients may also receive neoadjuvant chemotherapy prior to surgery, followed by further cycles of chemotherapy. As I mentioned earlier, many of these patients will relapse, and the commonest site of relapse is the lungs by far, and then they are eligible for second-line treatment. Here, the commonly used chemotherapy regimens are a combination of the alkylating agent ifosfamide and etoposide. That's a generally accepted second-line treatment. As you go further to third line and subsequent relapses, different lines of chemotherapy are used, are shown here. What are the general outcomes we've seen so far? What sort of evidence have we seen out in terms of disease-free survival? This was a study, independent academic study, AOST0221, which was published in 2015, which shows those patients who have relapsed first, so there's a first recurrence, in the lungs, and they've had complete resection of the pulmonary lesion from their lungs. These patients were given inhaled GM-CSF as part of treatment at that stage. The curves that you can see here are typical of what we've seen in this, in this, in osteosarcoma. The blue dotted line shows the event-free survival, and you can see here at 1 year, stage, typically it's around 20% one year event-free survival, which is pretty poor. There was also another study recently, published. This study looked at the role of anti-GD2 immunotherapy. This study looked at the combination of dinutuximab plus interleukin. Again, looking at those patients who had surgery for their pulmonary lesion, which has relapsed into the lung, and they looked at the disease-free survival or disease control rate as well as overall survival. The difference here is they included all relapses, not just first relapse, but also second, third, and more relapses. Unfortunately, they failed to meet the primary endpoint. As you can see here, the overall endpoint of disease control rate at 12 months was 30.7%. They were looking for 40% as their endpoint. Subsequently, when they looked at a subgroup analysis in those patients who just had their first relapse, you can see there on the top right-hand corner, they approached a disease control rate of 39%, which is close to 40%. This was a rationale here that, you know, if you choose the right group of patients and you look at those, there is some activity of anti-GD2 in osteosarcoma. This also provided a good rationale to look at the role of naxitamab in this tumor indication. I just wanted to show you're aware, Thomas mentioned earlier on that MSK are doing a study, MSK's sponsored study, called the 15096 study, looking at recurrent osteosarcoma, a relapse in the lung, and they're also following up these patients. This is, it's study I'll come on to the study in a second. The only caveat I'll say is just to indicate the patient population that's being included in the study. Ignore the bit where it says second-line chemotherapy treatment. That's not part of the study protocol. This is the study that MSK are doing. This is a phase II study involving three centers, MSK, MD Anderson, and CHLA. The recruitment status as of beginning of this month showed they reached 42 patients out of a target of 46. 36 of these patients represent only pulmonary-only relapse. The goal is to achieve at least 39 patients with pulmonary-only relapse, 'cause as you can see on the top right-hand corner, that's the primary endpoint for the study, which is event-free survival at 12 months in patients with pulmonary-only recurrence. Secondary endpoints, also looking at event-free survival for those patients with extra-pulmonary recurrence, such as soft tissue and neighboring regional areas. Secondary endpoints also include overall survival and safety. We anticipate the study will complete accrual, we hope by the end of quarter one in 2023. Hopefully, we then will be in a position, MSK will be in a position to publish some early efficacy data a year after that. Just on the bottom right-hand corner, you'll see what the ambition of the study is. The way the study was powered was to show a difference of 20% versus 40%. 20% disease-free survival is taken from the previous slide I showed you, where the disease-free survival from the AOST0221 was approximately 20%. Assuming that is the results that we will see, the aim here was to show a disease-free survival of at least 50% with a combination of naxitamab in this. We're hopefully, we're confident that we'll reach a positive endpoint in this. These are just the safety results. This study hasn't matured enough to show efficacy results, but these safety results were presented at the SIOP meeting in 2019. I don't know if you can see this at the back, but this was a study where the range of patients enrolled in this range from eight years to 29 years of age. Majority were male. As you can see in the bottom left-hand corner, most of these patients had relapsed to the lung, either one lung or both lungs, and almost all of them had chemotherapy and surgery. In terms of safety profile, there's really nothing remarkable here. What we saw in terms of immediate short-term and serious adverse events were very similar to what we've seen in the neuroblastoma indication. Toxicities as in the neuroblastoma indication, pain, hypotension, infusion reactions were typically seen in similar proportions, and there were no long-term or delayed toxicities seen. As I said, we have no efficacy results to show at this stage, but that will be presented at a later time. This leads us on to the Y-mAbs sponsored study. The intent here is to seek regulatory approval for use of naxitamab plus GM-CSF in recurrent osteosarcoma. The plan was to replicate the MSK study as far as possible, but also in order to seek regulatory approval, we needed a randomized control trial versus standard of care. We've had discussions with the FDA, the European Medicines Agency, and also the regulatory authorities in China, and we've got their input in terms of the study design to maximize the chances of regulatory approval. As you can see here, our expectation is this will be a global study involving sites, multiple sites in the US, in Europe, and in China. Our aim is to submit for IND in Q1 next year, and hopefully, our first patient will be recruited in this Q3 of next year. This is a study design for the study. We aim to recruit 140 subjects with recurrent osteosarcoma who are in second remission following complete surgical resection of their pulmonary lesions. These will be randomized 1-to-1 to receive either chemotherapy alone, and the standard chemotherapy for second-line treatment is ifosfamide and etoposide. This is following input, as I mentioned, from the US Advisory Board, COG, FDA, as well as other centers, other authorities in Europe and China. This will be compared to the same chemotherapy regimen plus naxitamab and GM-CSF. This is how this is designed, naxitamab will be given over five cycles at similar dose to what we've seen in neuroblastoma, which is 3 mg per kilo, day one, day three, and day five, and it'll be on a three-week cycle. Key inclusion criteria, I've already covered this. Age range will be minimum one year of age up to 40 years of age. Primary endpoint will be disease-free survival at one year. Secondary endpoints, including overall survival, one year and two-year disease-free survival, as well as safety. We have inbuilt two interim analysis events. First one after one-third of the events. This is an event-driven trial. The first interim we anticipate based on the number of events at a certain recruitment rate at Q1, Q2 2025. This will be primarily for futility and early stopping depending on the results that we see at this stage. There will be a second interim and possibility for us to reevaluate study sample size depending on the results we're seeing to ensure we get a positive result, and top-line results we anticipate to see sometime in 2026. The study is powered 80%, powered with alpha of 10%. Again, this was input from the regulatory authorities in terms of the statistical consideration. Our aim is to see at least a 20% difference between the standard chemotherapy arm and the chemotherapy plus naxitamab arm. It is quite ambitious expectation, but we're very excited and confident that, you know, we'll see if the prior trials are anything to go by some positive results, which will really be a breakthrough for a very difficult-to-treat cancer. This is just the participating sites, as I've alluded to earlier. There will be roughly a third of the patients recruited in the U.S., a third in Europe, and a third in China. Multiple centers across all of these countries. Changing tacks slightly, the last couple of slides. Thomas mentioned about the first-line study from MSK. That study was particularly looking at the use of naxitamab as part of a consolidation treatment, first-line treatment. That study will read out and hope to have a manuscript sub-submitted in the next few weeks. We'll come back to you at a later stage when we have the results of this. This particular study is a very exciting study. This is sponsored by Beat Childhood Cancer, which is a very important network group in the U.S. comprising of up to 50 sites who are affiliated with this group in the U.S. and Canada. They are looking at the role of naxitamab as part of frontline treatment in induction protocol to treat patients with newly diagnosed high-risk neuroblastoma. In that treatment regimen, they'll be looking at the use of five cycles of naxitamab plus GM-CSF in combination with chemotherapy as part of the induction treatment. The rationale for this is we've seen that the earlier you use immunotherapy, the greater the chances of improving overall survival. We know that disease-free survival, even if you just use immunotherapy at maintenance and consolidation, is still not where we would like it to be. There's a strong rationale if we're gonna make any headway into improving disease-free survival, there's a rationale to move the role of immunotherapy in the induction phase. That's really the aim of this. Primary endpoint is looking at VGPR plus rate, which is combination of very good partial response plus complete response, and they'll be comparing this to historical controls. Secondary endpoints includes objective response rate, PFS, and overall survival. Inclusion criteria, as I mentioned earlier, will be newly diagnosed high-risk neuroblastoma and patients with no prior systemic chemotherapy. Up to 50 sites are anticipated to participate in this study, and I'm glad to say the study has started, has opened up, and the first patient was recruited in September this year. Target is to enroll 76 patients. Last slide. Again, apologies if it's too small to read at the back, but this is just a study schema to indicate the study design. On the left-hand side shows you the induction chemotherapy protocol. These patients will get five cycles of chemotherapy as part of the induction treatment. These patients will be randomized, depending on the ALK mutation, and if they are positive for that mutation, they will receive an ALK inhibitor. Both those arms will receive naxitamab plus GM-CSF. After about four cycles, these patients will be eligible for surgery. Then after the five cycles, there will be an evaluation for response. If these patients have shown poor response, i.e., partial response, minor response, or no response, they are eligible on the right-hand side, as you can see here, for salvage chemotherapy, which is an additional three cycles of naxitamab plus chemotherapy. If they have had a successful response to the induction treatment on the left-hand side, these patients will go on to get standard consolidation treatment, which is combination radiotherapy, more intense chemotherapy, and stem cell transplant, and then following that, maintenance treatment as per the COG protocol. This is a study that it's gonna be very important for us, although it is sponsored by Beat Childhood Cancer. I think data that comes out of this study will be yet further evidence and support for use of anti-GD2 further in the earlier in the upstream of the lines of treatment of patients with neuroblastoma and hopefully improve outcomes for these patients. I'll stop there. Thank you for your time, and I'll I think we're open to questions. Thank you. Yeah. Hello? Does this? Yeah. Thank you, everyone. I guess we go to Q&A now, and we both have online and participants in here, so we'll just start from we'll work that way. First question to chat. Thank you for hosting this event and for taking my questions. I'm Charles Zhu from Guggenheim Securities. My first question perhaps on the SADA and perhaps also stepping a little bit into medical physics, but in addition to the initial potential imaging and PK data that you could disclose from your lead GD2 program, will you also potentially be able to share dosimetry data? Similar to that, you know, how are you thinking about from a dosimetry's perspective, the level of radiation dose that the tumors in your priority GD2 indications might require for therapeutic effect? Thanks. The dosimetry, of course, have been shared with FDA during the process, and will be shared at the international conferences later. I cannot share it with you today. What we've seen so far is that due to the PK optimization of the molecule, and we first add the radioactive payload when more than 90% of the protein is out of the body, we can dose very high amount, meaning that we can target efficaciously the tumor without hitting too much neither to the bone marrow or to the kidneys. We've also seen data for the liver. Normally, proteins are degraded in the liver that there's very low uptake in the liver, when we have the spacing between the protein administration and the radioactive payload. In conclusion, we can dose much higher with a 2-step procedure as we would be able to do with a 1-step procedure, like, for example, 131 iodine omburtamab. Got it. Great. Regarding my second question also on SADA, this time on the CD38, I'm kinda wondering how what was your thinking? How did you arrive at this target, and how are you thinking perhaps not only about the preclinical, scientific, and clinical rationale, but also the current commercial landscape for CD38 therapies? As a related follow-up, as a specific question, does your epitope overlap with that of DARZALEX or, you know, some of the other available therapies out there? Thank you. The sequencing bind to is not public yet, but it does not completely overlap with DARZALEX isotope, so it's not a DARZALEX molecule. What we do, we discussed a lot the indications, and we know for now there's a lot of an activity with the CD38. The naked antibody approach is predominantly from multiple myeloma, an indication that's not really rapidly dividing. There's been less success in lymphoma space, and also plasmacytoma space, for the CD38 antibodies as of now. I think the SADA has a potential here with a much more powerful payload administration to overcome the challenge for those indications. We are looking very actively to what is happening in the field, not only for naked antibody, but also antibody-drug conjugates and CAR T cells, of course, and bispecifics. We definitely think there's a lot of space for a radio immunotherapy approach in the relapsed refractory setting. The good thing here is that despite prior therapy, the CD38 target is not down-regulated significant on the cancer cells. We can actually repeat expose the patients for targeted therapy for CD38 with another payload, and this is what we're aiming for doing with the SADA. Great. Joseph Thome from Cowen and Company. Maybe just on osteosarcoma, how do the results, the final results of the MSK phase II kinda impact your thinking about the 205 study? Do the final results there impact your commitment to that, especially as it relates to that 50% EFS bar that you've set? Maybe second on the SADA platform, how far do you wanna take some of these assets before you think about partnering and licensing deals? Maybe I'll. Can you hear me? Yes. Maybe I'll take that first point initially. I think there's obviously enough rationale based on what we've seen from existing studies with dinutuximab and how they narrowly failed to meet the endpoint to indicate that we expect to see a positive impact of naxitamab. We're not able to comment on the MSK efficacy results, and that will read out when it will, but we are optimistic, based on the historical results, it will be positive. Just to address your second question, we are looking for validation in patients. As I said before, we can de-risk these programs very early on, and our strategy is to out-license larger indications, such as small cell lung cancer, and keep in-house smaller indications, niche indications, pediatric indications, to build a portfolio of those. I don't believe we have to take it through a full phase I, because of the de-risking possibility of these programs early on. Hey, Alec Stranahan from Bank of America. Good to be back in the Lotte Hotel for another Y-mAbs' R&D Day. It's been a few years. Three questions actually on SADA. Maybe I'll just go one by one. First is a clarifying question. In the study design for the GD2-SADA, you mentioned that the dose escalation for the SADA component's in Part A, and then the radioisotope is Part B. Could we potentially have a phase II dose selected after Part A, for the SADA component, or is that gonna be a refinement as the study goes on? I think we will look at it and refine it as study goes on. Definitely after Part A, we have a pretty good idea how the molecule performs in humans, how the PK profiles with different dosings look like in humans as compared to non-clinical animal models. Based on that, we will have a significant better way of predicting a recommended phase II dose. The recommended phase II dose is not a dose, it's a dose schedule because it's a combination of three things. It's a combination of the protein concentrations, spacing to the payload, and the amount of radioactivity we can add as a payload to within the safety of the patients. That's why we have this three-step procedure built in, and that we in a Part C, already in a phase I, have been allowed to have repeated dosings in patients. This also allows us there to get a better and first view on the outcomes because I think that you need to dose more than once with this technology to overcome these tumors. Okay. That's helpful. In my second question, you mentioned that the CMC package has been fully developed, FDA approved, for SADA. Do you see this actually accelerating time for new assets to enter the clinic? Would this be viewed, I guess, positively for any potential future partnerships? I think this is very positive that we are very able, first time ever with this, compound, to discuss with authorities and agree on a quality of the compound to be given to humans. What I shared with you was also very close collaboration between, different groups within Y-mAbs. We, within a two-year period, from we have a lead, actually can develop not only a CMC package, but a full non-clinical package and protocol developing as well. Okay, great. My last question, maybe for Thomas, you mentioned that you'd probably partner in larger indications and maybe look at failed phase III drugs to roll into the SADA platform. Are these drugs that maybe are against a great target but didn't have clinical efficacy on their own? Or are these, you know, ADCs or some other radiolabeled drugs that have failed? Maybe just some additional color around that. Yeah. I think it's drugs that have been proven safe in humans but couldn't be dosed up or failed in clinic. We saw Telix with Lilly and what they did. I mean, it's just along those lines. I think the platform is so uniquely differentiated also on a commercial level, so we can actually go after targets that most other radiopharmaceutical companies might not be able to because we use large infusion centers for the protein, and then they can send you to academia to get your isotopes. We have a very flexible possibility to do sponsored research agreements on failed targets, to do third-party optimizations, and outline some targets. I think we're gonna go out broad, but the gaining factor right now is in human data at this point in time. Thanks. Hi. Bill Maughan, Canaccord Genuity. I think with DANYELZA revenues, it's a lot easier to kinda get a grasp for the US potential. There's still a lot of conversation about these ex-US approvals. Can you give us any more context on how big an opportunity ex-US you think DANYELZA could grow to be? Well, I think, you know, I think you have to look at it in terms of number of patients and pricing power in the different markets. We haven't disclosed pricing in China, but we look at the Chinese opportunity as a major opportunity for DANYELZA ex-US. I think LATAM overall, with Brazil being the leading country where we already filed a BLA in September. We've actually turned around the first responses to Anvisa right now, so hopefully that will go well. If it goes well, it might be before October next year we get an approval. I think LATAM and China is the two major opportunities. We are obviously also just looking at providing access to children all over the world, and we're also chasing Japan as we speak and other markets. I would say significant opportunity for the company ex-US. You mentioned for SADA data that imaging data could be de-risking on a quicker timeframe from actual therapeutic data. Can you give us more color on what you'd be looking for in early imaging data that you think would help generate excitement and conviction in the program? I'll just give. You can add to it, but I'll. What we wanna see is we wanna see the protein and then the imaging dose light up the protein, so the uptake on the protein, and that depends on the time space between those two. That should be enough to validate the mechanism of action of the entire platform. I'll let Steen go deeper into details of that if you want. Yeah. I don't know how much deeper we should go, but I think it's very important to say that this molecule has not been in humans yet. This is the first time ever we have this two-step approach, and the good part is that we have a therapeutic approach, so we give a imaging dose first, meaning that 24 hours after you administer your radioactive payload, we actually will know whether or not you hit your target. I think this is really proving the concept, if we can have a biodistribution clean and a tumor uptake that we can see on a SPECT/CT scan, I think the principle for SADA has been demonstrated. Then from there on, it's safety and efficacy we look for in a dose escalation fashion, and that's why we perform a phase I dose escalation trial. Last question from me. In between the omburtamab CRL and the upcoming FDA meeting, to what level has there been any back and forth to the point where you can gauge sort of tone or content of the meeting coming up? Yeah, there hasn't been any back and forth. Fair enough. It's a CRL letter with deficiencies and advise on how we can address those deficiencies, and we're preparing a response book, and then we'll speak to them at a Type A meeting. It's just a process. We'll have to work through that. Understood. Thank you. Hey. Jeff Lopatin at Red Hook Asset Management. Thanks for hosting. Just a quick question. Just with respect to the BCC trial and frontline high-risk neuroblastoma, do we expect this to be a registrational trial, and how do we think about that in the context of having a historical control arm given recent, FDA actions towards perhaps you guys and others? Thank you. I'll take that. Yes, this is an investigator-sponsored study, of course. I think we'll have to come to a decision once we see some initial results coming through. We have had discussions with the BCC, who have been kind enough to allow us to use the data for purposes, you know, for regulatory approval if needed, if appropriate. I think we'll just have to wait until that results come through. What are the chances that this will be accepted by the FDA for regulatory approval? I guess it depends on the degree of benefit seen, the quality of the data that they've conducted, and historical control is a thorny issue with the FDA, as we know. I think it'll really depend on how comparable the patient population they've selected and if there's substantial evidence seen in this comparison. I think it's possible. We'll have to see exactly to what extent the benefit has been seen before we judge that. Also adding, you know, we're obviously also looking at tumor responses with DANYELZA. It's a little different because you're using it up front in induction phase where you get five cycles of chemotherapy to shrink the tumor. Now we're adding DANYELZA to that. We actually are seeing the difference between a patient who doesn't get DANYELZA versus a patient who gets DANYELZA and chemotherapy up front. We should definitely see tumor responses before surgery. That helps us with the FDA. Yeah, I mean, typically the response is seen at the induction around 40% responses, and we're hoping to see in this study up to 60% is what the aim is. If we get anywhere close to that, this will be a significant persuasive element for this to be adopted as part of induction protocols. Whether or not it'll be accepted with the FDA, we'll have to come across that bridge when we come to it. Hey, guys. Robert Burns from H.C. Wainwright. One question on your CD38 SADA. Obviously outside of multiple myeloma, CD38 expression is significantly lower like CLL or DLBCL. I'm sort of curious what you're viewing as the benchmark in that... in those two lymphoma populations and leukemia populations. Thinking about the multiple myeloma opportunity, considering the data we saw from Takeda's modakafusp alfa at ASH this year, I'm sort of curious how you're viewing that as a competitor to the CD38 SADA and then the CD38 CAR T agents and where you see the SADA sort of fitting into that myeloma paradigm. I think that the benefit from the CD38-SADA is that it has a powerful payload, and I agree that the lymphoma space, they have less expression as compared to multiple myeloma. So far in non-clinical in vivo studies, we're actually able to treat different lymphoma cell lines in a xenograft model. We are confident that we can see some activity. Of course, this is why we do the clinical testing. Plasmacytoma also is an indication that are rather radio sensitive and would benefit from radioactive payload. Multiple myeloma space is highly crowded for the moment, not only for CAR T, but CAR T is very difficult to administer and for the selected patients. You also have bispecifics and ADCs, and of course you have the naked antibody, two naked antibody approved. The myeloma space is much crowded. The benefit from a myeloma patient is that it's very little chemotherapy they receive. Even though we had three or four lines of therapy administered, they're still in quite good shape and can benefit from having a 5th line of therapy. Also the benefit of a radioimmunotherapy as compared to a naked antibody is we don't need the patient's immune system to be intact anymore. We just need the target to be there in order for us to deliver the payload. As such, the relapsed/refractory setting still is where we can. Gain evidence of efficacy with the molecule, both in lymphoma and most likely also in the myeloma space. That's to be seen. Hi, this is Taylor from Tessa Romero's team at JPMorgan. I have a quick question. For both DANYELZA and the SADA platform, you've talked about looking for potential partners to move larger indications forward, and in DANYELZA's case, supporting investigator-sponsored requests. I was just wondering, how much interest have you seen for both DANYELZA and the SADA platform from potential partners here? Are there any characteristics for potential partners that you're specifically looking for for each of these? I'll take the first, and then I'll let you talk about ISS. you know, overall partnerships, initially we would like to work with people we can leverage. there's a select handful of great radiopharmaceutical companies out there that we are, of course, talking to. I can't give more details than that. On DANYELZA, what I can tell you, gating factor right now for us is in human data, which was also put us in a stronger position once we're able to de-risk that. We're happy we ended up where we are now. DANYELZA, you know, we are not spending budget on these larger indications even though we would like to, we have chosen to use a strategy of getting some ISS proof of concept. DANYELZA was developed as a scientific protocol initially at MSK, and it's dosing Monday, Wednesday, Friday, and you would never go into a large adult indication with that kind of schedule. We'd have to do a ISS study where we re-dose it according to its half-life, maybe day one, day eight, maybe even day one, day 16. Our strategy is to do it through an ISS, and I think Vignesh, you can comment on the interest, which is we see that. Yeah. Yes. We have seen interest for multiple adult cancers. For example, there are two studies in triple-negative breast cancer. One is a preclinical, one is a phase I clinical in combination with chemo in breast cancer. We've also had a request in the past in melanoma and one also in combination with another targeted agent for use in soft tissue sarcomas. There is interest out there because of the rationale for GD2 as a target. Where the design makes sense and where it fits with our strategic area we wanna go, we're looking to support these studies where we can. Okay, great. Thanks for taking my question. Hey, Alec Stranahan from Bank of America again. One question on DANYELZA pricing in China. I appreciate maybe you can't give the details yet, but, you know, I wanted to ask how you're sort of approaching market access, whether you would seek to get it added to the NRDL at some point, if that even makes sense in a smaller indication like this, and, you know, how you're sort of setting pricing up if that is a consideration. Yeah, that's a good question. Initially, we have a strategy that SciClone has worked out. They've been in the market since 1996, and they have a very established commercial infrastructure. Our strategy is initially, I believe it's 3 years before you seek reimbursement, across the board nationally, and that will obviously induce a price reduction when you get there. Initially, the first 3 years, I don't think, that's in the plans. Then once volume, you reach a certain volume, then you go in. Okay. I think you had mentioned previously, that there has been sort of, you know, some use in China, pre-approval. Could you maybe talk about the, you know, sort of the adoption there and the enthusiasm around the drug? Well, we've treated patients in the pilot zone. Once you have an FDA-approved product, they will allow you to treat patients there. I think the clinical experience, I actually think, Vignesh, you can maybe give a brief on how successful that has been. Yes. There's been no shortage of interest in the use of DANYELZA as part of a compassionate use or expanded access in those small selection of hospitals. We've had patients being recruited for over a year now. There's 30-plus patients in the last 12 months alone that have been enrolled, and we've had a very good experience. I think the early few weeks, what we realized, is close collaboration with SciClone to educate and inform the physicians about the safe and appropriate use of DANYELZA to minimize any toxicities, et cetera. Once we got over that, we got into a kind of a rhythm because the physicians started to get a lot of expertise, and they were able to train the trainers, in other words. As we've gone over the last 12 months or so, the incidence of adverse events has plateaued or, if anything, reduced. They're able to manage the patients better, they're seeing positive response feedback from the physicians. I think it's all looking good. Certainly from a clinical point of view, there seems to be a positive feedback from the physicians and, if anything, we're holding back until the launch before it's opened up to other centers. The key for success here is to manage the patient education, physician education in a controlled fashion because of the profile of naxitamab. When you do that, the experience with the physicians is very positive, and that's the key to success here. We have regular interactions with SciClone, our medical and our safety team with their counterparts, and it's working really, really well. We're very excited about the potential launch or the launch, I should say, of DANYELZA in China. Thank you. Robert Burns from H.C. Wainwright again. You know, Thomas, your predecessor quoted that there are roughly 2,000 newly diagnosed neuroblastoma patients in China annually, and you said earlier that, you know, SciClone's gonna target roughly 40 hospitals in 2023 for penetration into that market. I'm sort of curious about the number of patients with neuroblastoma that are treated in those hospitals, and do you see a similar flow through rate from the front line into the second line setting as you do in the U.S. in China? I think in China it's a completely different market than in the U.S. First of all, you know, chemo combination is not highly developed there as it is in the U.S. as a standard in the U.S. Second, I think we have a great advantage being outpatient coming to China, to these hospitals. Third, the number of patients, yeah, I think that number is right. There is a large number of patients. We've seen QARZIBA has been approved there. We've seen the number of patients they have treated. So I think the strategy for us is to go in and add on a 203 study. I don't know if you remember the hits data that was created for ASCO. You know, that data's not over there, so we are actually planning with SciClone to add a 203 study on non-commercial patients, in order not to cannibalize that and then get that experience out into physicians in all these hospitals. I think it's fairly... it's fair to say that it's also centers of excellence, so as the same framework as it is in the U.S. and there's some sites that are communicating with U.S. sites in terms of experience and all the conferences and so forth. It's a different index than it was for us when we launched in the U.S. Very, very different. Hey, Thomas. Okay. I think, we look forward to seeing you at JPM, where we will have a presentation and give an update overall on the company. We hope to give you some guidance there and give you an update on the overall corporate strategy going forward, and we'll have, some more, things to share with you then. This was a handy day today and, thanks very much for spending time with us. Thank you.