All right, good afternoon, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference, and sticking around for the last day of the conference. I'm Mike Schultz, one of the biotech analysts here, and it's my pleasure to introduce, Mike Rossi, CEO from Y-mAbs Therapeutics. Just a reminder, format for today is a fireside chat, so if anyone has any questions, please feel free to raise your hand, and we can address them in our discussion. But before we get started, I just need to read a quick disclaimer. "For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative." And with that, we can finally get started here. Thanks, Mike. So, Mike, thanks for sharing your time with us today. And maybe I'll just hand it over to you to kick off with some introductory comments, and then we can hop in the Q&A. Sure. Well, thank you. So I'm CEO of Y-mAbs. We're a commercial-stage biotech company with a current product in the market called DANYELZA, and it's an anti-GD2 product that is a pediatric oncology product that addresses high-risk relapsed refractory neuroblastoma in children. Now, we also have a pipeline of radiopharmaceuticals, which we'll discuss today, in addition to... But, you know, a very solid company. We're a self-funding biotech, which is highly unusual. We've got cash runway into 2027 with very minimal cash burn. So our DANYELZA product and its success is allowing us to really invest in our pipeline. And we've had some recent leadership changes. I joined the organization almost a year ago. I've had the opportunity to bring in a new general counsel, a new head of drug development, who has more than forty years of experience in developing drugs in the radiopharmaceutical space, as well as a new CFO, who has in-depth large pharma, as well as biotech experience, so we're really building out the team and focused on our growth path for the future. Okay. Well, great, thanks for that introduction, and thought maybe we'd just start with DANYELZA. As you mentioned, it's your, your product that's currently approved, it's been on the market for a few years. Maybe just talk about, you know, what you've learned through the launch and some of the recent sort of changes you've made at the end of last year to sort of keep driving that growth. Yeah, so it's a unique product. It came out of Memorial Sloan Kettering, and really meeting an unmet need in pediatric neuroblastoma, which is the most common cancer in children. So for us, it's really galvanized the organization to focus on what matters, which is patients. We've had the opportunity. We're in our third full year of launch. The product has been continuously growing, and our main competitor had a six-year head start on us, so we're eating away at them and with some distinct advantages, where we really have learned where to take this product. And more importantly, the product has some great data. It's the only humanized antibody, which is fantastic in children. And also, you can treat children in the outpatient setting. And the outpatient setting has meant so much to parents to be able to take their children home at night versus spending a week in the hospital at a time and with these infusions. So you know, we we've done a nice job of reaching out and expanding its use and continue to grow the product. Yep. Can you maybe talk about some of the recent changes you've made at the end of last year to... Or those fine-tuning adjustments? Yeah. So we focused the organization and restructured the organization to really focus in two areas. One is maximizing DANYELZA and increasing its clinical and commercial reach, as well as fine-tuning the organization to focus on our radiopharmaceutical pipeline development. We've got investment in the lifecycle management of DANYELZA to continue to expand its labeling indication, and we've got a very high experienced sales force that's focused in neuroblastoma, as well as a medical team with very in-depth experience. And, you know, we're continuing to invest in neuroblastoma, which leads us to the SADA platform and our- Mm-hmm. - our first product in the radiopharmaceutical pipeline, also in the GD2 space. Yep. And maybe just a couple follow-up questions just on DANYELZA, just the quarterly variability in sales and kind of what's driving that. Are there ways to sort of smooth that out in the future? Yeah. So what we have is we have a US market and an ex-US market, so roughly an eighty-twenty split. What we've seen is, excuse me, continuous growth in our US business. And some of that you'll see tapering off as some competitive products come in, as well as competing studies, clinical studies from both us as well as competitors. But what we've seen is nice, steady US growth. We've also expanded in the ex-US space, and we continue to add on additional locations with partners. I think the lumpiness that you see from an ex-US perspective is really twofold. It's new markets coming in, so some stocking of material- Mm-hmm ... and then, it'll come in in waves. So, you know, we launched in China last year. We send entire batches to China to qualify it in country. So you'll see kind of big dumps of material. Where you'll see some flattening out in areas where we have partnership or royalty agreements, as the launch is progressing forward, you'll see that flattening out, and the royalty stream becomes a little bit more predictable. But you'll continue to see kind of this, these ebbs and flows in the stock-in s. Yep. You mentioned sort of expanding into China. Maybe you can talk a little bit about, you know, what's the market opportunity look like there, and then beyond that, just other geographic opportunities to continue to expand the use of DANYELZA. Yeah, so China is obviously one of the biggest markets and puts us in a very favorable position for volume growth. We have a very good partner in China. We've also just had a Hong Kong approval. So we're continuing to expand in the Far East. And the opportunity is quite. It's actually larger than the US from a volume perspective. Overall, from a revenue perspective, being in a revenue share environment, it's a little bit different on the mix. However, we've also had approvals and launches in the second quarter in Mexico and Brazil, and we continue to look for opportunities outside of that. There will be, you know, additional territories we consider. We also have direct-to-patient on a named-patient basis in Europe for access, since we don't currently have a European approval. Yep. Got you. You're also working on, you know, expanding the label in a couple different areas. Maybe you can start with the first, maybe front line neuroblastoma and kind of the status there and next updates. Yeah. So in front line neuroblastoma, we're doing some work with BCC, which is Beat Childhood Cancer. And, you know, there's an ongoing clinical trial that we're continuing to expand. So it's an opportunity for us to look at potentially getting ahead of bone marrow transplant and supplanting that. For us, we continue to invest in neuroblastoma, and BCC has been a very good partner in that. And again, a lot of the standard of care in the U.S. has been bone marrow transplant, so this is getting out ahead of that and looking that DANYELZA's labeling allows us to focus on bone and bone marrow, and it's the only anti-GD2 product with that indication. So we continue to invest to move that forward. I think from a label expansion point of view, first things first is- Yep is to get physicians using it as part of the clinical trial, understand what the data looks like, and then make some decisions on what the labeling update looks like from there. Yep. So can you use the ongoing study to sort of, you know, for regulatory purposes, or would you have to run a separate study, or unclear right now? It depends how it expands. Yeah. Right now, it's not designed necessarily for label expansion. It's more experience. Yep. And from that, we'll make some decisions whether we need to expand that trial and, you know, take it out further into a randomized registration trial, or if you see physicians getting comfortable in using it and understanding what the next steps may be to actually expand the label- Yep - not just the usage of it. Yep, makes sense, and you also have, you're looking to expand into osteosarcoma. I think it's a study with MSK. Maybe just talk a little bit about that and where you are and next steps. Sure. So the MSK will be presenting that data in November, and we've had some good results come out of that. The study itself missed its primary endpoint by two patients, but there's a lot of opportunity within that study to learn how we want to move it forward in osteosarcoma. Interesting enough, we're gaining a lot of experience with our radiopharmaceutical and osteosarcoma as well, and understanding which patients express and which don't. Mm-hmm. We need to go back and really look at that data and understand patient selection will be extremely important. Yeah. But in the trial, we had 14 responding patients, roughly a 37% response rate. Again, a very small trial, but it actually showed significant improvement over standard of care, which is about 20%. So, you know, we'll look at that and make the decision on investing into an osteosarcoma study, registration study to- Yeah - Expand the labeling. Any other areas of label expansion you're considering for DANYELZA? We've got some investigator-initiated trials that we're working on, looking at things like Ewing sarcoma, as well as triple-negative breast. Okay, great. Maybe we can switch to your SADA platform, which I think there's probably a lot of interest there. Maybe just talk about your platform, and some of the challenges you see in the radiotherapy space and how you're trying to address those. So my background, I've spent the last 30-plus years in the targeted radiotherapy space. So this is an exciting time for radiotherapy and the expansion that we've seen and the ability to really target disease. But there's three areas that are challenging in radiotherapy. One is making sure that you've got the specificity for the tumor and minimizing off-target toxicity in the patient. So really, patient focus first, make sure it's delivering the radiation where it should be. And systemic radiotherapy is delivered right at the cell membrane, so it's really a fantastic treatment with a lot of opportunities. The second is physician participation. Part of the challenge in this space is the physicians that are treating the patients and taking care of the patients today can't necessarily prescribe or administer radiotherapies, as it's generally left to an authorized nuclear physician to do that. So it's 100% referral at this point, and then third is the infrastructure needed, and that's both at the hospital level as well as the manufacturing of isotopes, manufacturing the radiopharmaceuticals, because regular pharmaceutical plants aren't set up to deal with radiation and radiopharmaceuticals. As we look at this platform, you know, there's an opportunity in a pre-targeting SADA that addresses all three of these. So just an overall view of the platform itself, how we're differentiated. The current products in the market are prelabeled or pre-tagged conjugates. So the drug is actually radioactive when it's injected. That creates some issues in that it's circulating as a radioisotope. It's, it's irradiating areas potentially that you don't want to irradiate it, and it, it limits specificity. It also, it's a melting ice cube, so it's like shipping an ice cube across the country in a non-refrigerated truck because it's gonna continue to decay and get smaller and smaller and smaller over a period of time. When we look at all of these things, our pre-targeting platform is exactly that. The drug itself is injected as a non-radioactive drug, and it actually paints the tumor at the receptors. Why that's important is you inject the drug, it's non-radioactive, it circulates, binds to the tumor, and then what doesn't bind is eliminated before the radioactivity comes in.... The radioactivity is then injected, and it seeks out those tumors on the binding site from the drug. So it allows a concentration on the tumor and rapid elimination from outside of the tumor. So it addresses the targeting within the patient, allows the oncologists, endocrinologists, urologists, to actually do the drug infusion by utilizing their existing infrastructure, so their outpatient infusion centers, their inpatient infusion centers, their offices, because it's non-radioactive. And then the patient just needs to go to nuclear medicine for the isotope injection, which becomes a much better throughput than a long infusion in a theranostics suite that there's not enough of them to deliver. So it solves these issues. The other big component of this is it better utilizes the half-life of the isotope, because we don't need a facility to assemble the drug to the isotope, because that actually happens in the patient. Where these pre-targeted technologies, the isotopes have to get shipped in from around the world. Takes a few days to do that, a few days to manufacture it, another day to ship it, another day to inject it, and it basically burns half of the product before it reaches the patient, and all that infrastructure is needed to put that together, where in the pre-targeting, it's a much more simplified and elegant process. Yep. Can you talk about your choice of targets? You know, I think you're looking at a few, but maybe just talk about the targets and maybe why you chose them and why it makes sense for this approach? Yeah. So interesting enough, the SADA technology or the self-assembly and disassembly of the pre-targeting radioimmuno therapy was licensed in from Memorial Sloan Kettering and MIT in 2020. By 2023, less than three years later, we were in patients, so it was a very fast turnaround. And we were able to do that because we utilized our DANYELZA product, which is naxitamab, which is an anti-GD2 product. We used a sequence from that to attach it, a sequence from the antibody to create the anti-GD2 anti-tumor component of the SADA and get into patients. So it was a fast approach to use on really a non-validated target in the radiopharmaceutical space, but get there quickly, and it was a fail-fast mentality. Mm. Because this is the first radiotherapeutic in humans that is an in vivo-tagged radiopharmaceutical. So that was part of the reason. Also, our investment in neuroblastoma, we wanted to continue to move that forward with additional choices for adults and for children, because many indications actually express GD2, and it created an opportunity for us to really validate and understand the system. Mm. The second product we brought in was our CD38, which we're recruiting for patients now, so that's an open trial as well, so two clinical trials that are currently open in the SADA space. We had a lot of experience with our Denmark team that was part of the development of a CD38 product, so we were able to take that knowledge from the CD38 sequence, get that onto our SADA platform, and get in to validate this in circulating tumors. Mm. Our first two were a bit opportunistic as a company to get them into clinic quickly. Yeah. Validate the platform, really understand it, so now we can increase our speed and add additional targets and focusing on some bigger indications. You mentioned sort of non-validated radiotherapy targets. Maybe just talk about, outside of PSMA, why it's been so challenging to sort of have success with these other targets. Is it more target related, or is it more approach related, like antibodies versus small molecules, or what's... If there's an answer to that question, there may not be, but. There's an opinion. Yeah. Okay. So, you know, and I'll give mine. Sure. So I dosed my first patient in 1992, and it was a patient that was a prostate cancer patient, who was end of life and was really struggling with pain and pain control. You know, I'm a pharmacist by education, a nuclear pharmacist by choice. I did an internship, learned a lot about nuclear pharmacy, and I was doing an oncology residency, and I had this patient, and I knew of one of the first palliative treatments for bone cancer. I was able to convince his physician and him that it may be an opportunity to treat him in a way that could give him better quality of life. Was able to acquire the product under compassionate use from Amersham at the time, and shipped it in and saw great results in that patient and their quality of life. It focused my career in doing what I could in this therapy space to have that kind of impact on more than one patient. We've had successful products. The first theranostic was introduced in the early 1940s for thyroid cancer, and it's still used today as it was, I-131. It's really the gold standard of how these products should work, safety, efficacy. We've gotten into a few palliative agents for bone therapy. We tried fully tagged antibodies in the late 1990s, which actually had great success, but also great toxicity. Mm ... because of that circulating time. Mm-hmm. And this was in the non-Hodgkin's space as well. But commercially, they weren't as successful as regular pharmaceuticals. So these are higher value, lower volume products, and there wasn't necessarily the appetite or the technology. And as we moved forward, we moved into our first alpha being the Xofigo by Bayer. It was another one that was focused on more palliation, but also saw some overall life extension. The first step forward was getting lutetium dotatate into the market for neuroendocrine patients, and we saw some great success with that. Albeit a rare disease, I said it was a good, bad product to start with. Mm-hmm. It's always tough to start with a rare disease because it's limited in how many patients, but it was a great product to start with because patients have a long life expectancy, and you get to see the safety profile of the product over a long period of time, and physicians got very comfortable that systemic radiotherapy was safe and effective, and they were less concerned than going into prostate cancer, which is now a big indication. Mm-hmm. Right? You weren't going to get five-year survival data on patients with an eight-month- Yeah Life expectancy. So I think now what's exciting is there's been repetition of success and what the expectation is when you can deliver the radioactivity to the tumor. Mm-hmm. So I think big pharma's taking notice. There's ways to commercialize this to recover your investment, and so the momentum is picking up, and we've seen four big pharma companies enter this space in the last, you know, couple years. Yeah. It's really an opportunity for us to continue to invest, continue to push forward, and look for opportunities to really treat these receptor-modulated diseases. Yeah. Can you share your thoughts just on payload, how you're thinking with your products? Can you easily interchange the isotopes you choose? Yeah, so our platform is unique in the fact that we're isotope agnostic. We have. If you bifurcate the platform, you have your non-radioactive drugs on one side and your isotopes on the other side. The drugs will each develop based on a specific tumor target or a receptor, depending, you know, if you're in oncology or beyond oncology. But the isotopes will be, we'll say, generic to those, and any of the isotopes will be able to bind to those drugs. So we'll move forward with development in the diagnostic space as well as in the therapeutic space, both in alphas and betas, that will allow physicians to choose. Also, based on the data that we see, there may be one isotope that lends itself better to a certain disease or a certain tumor or a certain target, and we'll be able to focus on that from a clinical study point of view to get the best results for the patient. Yeah. What's the current thinking on the right tumors for alphas versus betas? A lot of clinical work needs to get done. Right, in alpha and beta, when you look at it, they're both very effective, and in different ways. So if you, there's a question of, do you use beta first for bulkier- Right - disease, then alpha for refractory? Is alpha the right choice for micrometastatic disease- Mm-hmm - where the path length is very short? Also, based on where it's located. I think the jury's still out on that. I think there's going to be a place for both alphas and betas. And also, as you look at its distribution throughout a tumor, you know, potentially, if you can't penetrate the tumor throughout, beta may be a better choice, and it's like peeling an onion. Yeah. So you keep attaching it to the outside, it's radiating and then creating a radiation field. If it's well perfused, and you can get the alphas throughout, you get a lot of double stranded breaks. Mm-hmm. You can create a situation where you're really having a major impact on the patient, potentially getting to more curative states. Yeah. With the micrometastatic disease, where you're treating a few cells at a time, alphas make a lot of sense because the path length is so short. Makes sense. Maybe we can focus now on your phase 1 ongoing program for GD2 SADA. Maybe just talk about the study design. I know there's three different parts, but maybe help us understand the sequence of those sort of parts and what you need to learn at each step as you move forward. Sure. So the study was designed to learn about the platform, and it was really to be first-in-human s, and to understand in a two-step approach, you have several variables. The first variable is how much protein is enough protein to paint the tumor without giving excess that you're creating high peak levels in the blood for extended periods of time? So the goal is to inject the isotope while the tumor is painted, and there's minimal amounts in the blood, so you don't get that circulating tagged radiopharmaceutical. So our study is designed in Part A, to first determine what the safety of the protein is. This was a first-in-human study, so you have to go slow and be careful. We've dosed our first 17 patients without any dose limiting toxicity, so we feel really good about the safety of the product. The second component is then optimizing how much protein is enough protein. The second component is, what is the window in which you're going to inject that radioactivity to maximize what goes on to the tumor? Part A is designed to escalate the protein, determine what the right protein is. When we find that, what's the right window for injection? Mm-hmm. And once that's determined, those will be two fixed variables that we take into Part B, which is then dose escalating the isotope itself and giving up to two cycles of it, because we know that it takes more than one cycle for efficacy, so we want to see how the patient responds to multiple cycles. Once that's determined, on how much radioactivity we can actually load onto that tumor to maximize absorbed dose, our Part C is doing up to five cycles at those higher dose levels, and that'll give us a good efficacy signal at that point of, Do you have something that you can continue forward with? Maybe you can talk about sort of the intervals you're testing and thinking, and kind of, you know, if you've sort of solved that piece of the puzzle yet? I think we're getting closer. Yeah. So based on the animal model, we took it to clinic, and we wanted to err on the safe side. So the animal model, as it translated into humans, we're looking at roughly a one milligram per kilogram protein load and roughly a two-day window to inject the isotope. So we started at a third of that dose from a protein, and we started out at a five-day injection window just to make sure we did no harm, and it was to kind of find that optimal area. So our first. We've done five cohorts so far, and our first two cohorts were at 0.3 milligram per kilogram, so that was a third of the anticipated dose. And we did a five-day window, followed by a two-day window in the second cohort, again to look at what those tagging ratios. Then we started escalating the protein. Our next one was at one milligram per kilogram in a five-day window, and then a three milligram per kilogram at a five-day window, so we had a third of the dose, the target dose, and three x that dose to get the information, and we could take that up to ten milligrams per kilogram as part of the clinical study. What we saw is potentially that we already had enough protein, so we actually backed it down into our fifth cohort at one milligram per kilogram and shortened the window to four days. Now we're looking at shortening the window even further as we're fine-tuning it in to say what is optimal and having enough protein, and then a short enough window that you've cleared all of the circulating SADA, and you've put the isotope on the tumor while it's at its optimal amount before it starts to fall off. Yep. And you've mentioned sort of sharing an update from those activities later this year. Maybe just talk about, you know, what we should expect there. Yeah. I think one of the things that we wanted to do is, because it's a safety study, normally there's not a lot to share. Yeah. But in our case, we added the radioactivity to it, so we can visualize where it goes. Mm-hmm. What that looks like and what we've learned. So we're compiling all of that. Our plan at the end is to take all of the patients from Part A and present all of the data, what we learned on which tumors express, which do not, how do you patient select? More importantly, what the safety of the protein is, and then what we've learned from an optimal protein and window. We've made some protocol modifications throughout as we're learning. Mm-hmm. And we're also adding in. You know, we had a request to add in adult neuroblastoma, and there's an unmet need there, so we opened the trial. We're adding an adult neuroblastoma for the next cohort, which we know is a high-expressing GD2 tumor. And so that'll give us some additional information, which will then allow us to complete the IND for our pediatric trial focused on pediatric neuroblastoma, because we didn't want to start there. Yeah. Once we close out Part A, we plan on reporting all of that data in early 2025. Yeah ... and what we've learned from the Part A as we roll into Part B. Yep. Okay. And as you move into Part B, you know, when could you sort of complete that stage and move into Part C, potentially? I think as we look at this, the expectation is we'll move right into recruiting as soon as we close out Part A. Yep. So we'll recruit and start dosing in 2025. And, you know, if things go well, we would expect to be able to more or less recruit that within 2025 and report- Yep after we see some of the last instances. Makes sense. Once you sort of have this dosing figured out for the GD2 SADA, is that sort of, you know, would be standard for the platform moving forward? In other words, when you move to your next program, which I think is the CD38, you know, would you sort of... Could you shorten that timeframe? Would there be some tweaking of the interval or the dose, et cetera? Yeah. I think we've learned a lot from this. And again, as a first-in-human, we are taking a lot of that data and information, and we're applying it to what the next protocols are, and looking for an opportunity to speed the dosing. And it's always challenging the first few patients, anytime you have a brand-new technology, a brand-new platform, to recruit those first two patients. What we're seeing now is physicians are comfortable with the safety of it. So the last cohort we opened, we had the next three patients identified in the first week it was open. So our next thing from just opening our 1201 trial, which is a CD38, we're searching for that first patient now. And it's a little bit more challenging space, right, in the non-Hodgkin's space. Mm-hmm. However, you know, we expect to have multiple sites up and running shortly. Right now we have one, and we want to get that to six within the next month or two. Yeah. And that'll allow us to then seek out those patients and expedite it, and again, shorten what the overall protocol looks like. Our current safety window, our evaluation window is six weeks with our 1001. We were able to get four weeks with the 1201 based on what we saw in the safety in this. So we are taking those learnings and shortening the timeframes. Yep. Makes sense. And what about just read-through? You know, if you're successful with your first program, you know, that, you know, do you de-risk, you know, the rest of the programs, or how do you think about that? Yeah. I think, you know, the key is getting the clinical data to match the preclinical. So the more data we have across multiple targets, the more opportunities we have to even accelerate those. Mm-hmm. So the SADA platform is unique because it is just that, it's a platform. Each of the structures are relatively the same as a tetramer. All will have the anti-DOTA binding site on, and what we're changing out is the target. So we have a GD2 target, we have a CD38. We're also working on HER2 B7-H3. There's additional that are- Mm-hmm ... in preclinical that we'll bring forward, but the more we learn from these, the faster we can go and the more products we can bring to clinic. Yeah. Maybe just talk a little bit about the timeframes for these other targets, like where are you at with CD38 and then the, those other two you mentioned? Yeah. So CD38, the trial's open, so that's ready to go. That's recruiting. We expect first-in-human shortly. Yep. When we look at B7-H3 and HER2, they're in lead candidate selection, and getting those lead candidates and manufactured moves it into the IND process. So we're looking at right now targeting the end of 2025 for IND. But, you know, we're taking this quarter and all of what we've learned from our 1001 and looking at a universe of targets that make sense. So I think toward the end of the year, you'll see an update from us on what isotopes, what targets- Mm-hmm ... and what timelines. Okay. We'll be truing that up, and I think you'll be quite pleased with some of the progress that's been made already. Yep. Yep. Looking forward to that. And I guess how are you thinking about just partnerships? You know, you keep pushing these programs forward, you're looking to partner and, you know, what point in time makes the most sense? Yeah. So, you know, we've got two different things, right? We have our platform, which is the foundation of all that we're going to do, and then there's the drugs or the programs that it's going to produce. There's going to be products that make sense for us to run right through commercialization. There'll be others that make sense for others to take in and partner. So we're in discussion with others that are interested in specific targets that we may not be interested in. Mm-hmm. Even something like a HER2, it's a crowded space. Yeah. There's potentially partners out there that can see this as an extension of what they're currently doing, an opportunity to partner with some IO or ADCs. You know, the interesting thing on the radiopharmaceuticals is not only is it a standalone therapy, it's potentially sequenced well with something like an ADC- Mm-hmm ... or an IO. If you radiosensitize those cells first and then come in with an ADC or an IO, does that make them more effective? Or a DNA damage repair inhibitor. Yeah. For ours, our mechanism of action is damaging the DNA with the isotope coming in on top with something else. I think a lot of the partners are looking at this of, you know, is it something you use prior to an ADC or an IO? Yep. Is it something you use afterward, after a patient begins to progress, radiosensitize them, and come back to that therapy, or potentially, a DNA damage repair inhibitor as a follow-on to maintain response? Yeah. I think there's a lot of partnership and BD opportunities, but ultimately, you know, we see this platform as a way to produce a lot of drugs in a short period of time. Yeah. Okay, makes sense. A lot to look forward to in the future here. So looks like we're just about out of time, so why don't we end it there? Thanks so much, Mike. Appreciate your time. Mike, always a pleasure. Thanks.