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

Good afternoon, everyone, and thank you for joining us here today. It is my pleasure to introduce Mike Rossi, President and CEO of Y-mAbs who will be leading the presentation today; and Bo Kruse, CFO, who will be joining Mike in the Q&A. With that, I'll hand it over to Mike. Thank you, Mike, for joining us here today and sharing your story with us.

Well, thank you very much, and welcome to everyone. Thank you very much for attending our presentation of Y-mAbs Technologies -- Y-mAbs Therapeutics, excuse me. My name is Mike Rossi. I recently joined in November as the President and CEO. So, I'm looking forward to taking you through our novel pretargeted radiopharmaceutical platform, as well as our antibody-based therapy DANYELZA. So thank you for attending. As a disclaimer, please note that any of the forward-looking statements may be made today during our presentation and our disclaimer is available on our Investor Relations website. So Y-mAbs was founded in 2015 with the specific clear goal in mind to ensure and provide therapies for both pediatric and adult patients across the globe. Since then, we've been able to really advance our novel platform and move forward on both our monoclonal antibody commercialized product, DANYELZA, which is the first humanized antibody for relapsed/refractory high-risk neuroblastoma, as well as continuing to develop our SADA platform, which is a self-assembly and disassembly tetramer that's used to [ tag ] radioactivity to specific targeted tumors within the body. The Radioimmune platform is exciting. As we know, radiopharmaceuticals are growing in popularity. We see the effect of it, and I think we're well positioned to have a great discussion today on what that means for the future of the organization. More importantly, we also have DANYELZA. And DANYELZA is our monoclonal antibody that is reaching children today with the high-risk neuroblastoma. We've marketed that product, now we're low 2 years past launch, growing that product, both in the US and ex-US and continue to grow that across the globe and move it earlier and earlier in the treatment cycle. We've got some great milestones coming this year, which is going to be very exciting. First and foremost, we have the initiation or we'll have a readout later in the year of our Part A of our Phase 1 GD2-SADA readout. I'll share a little bit of that data today. And the rest of it will be shared in totality as we move forward toward the end of the year at a medical conference. We'll also have our CD38-SADA. That will be initiated in the first half of this year. We have an approved IND and are working to recruit our first patient. So that will be 2 of the SADA targets in first in human in the US. Additionally, we have some MSK data coming at the end of the year on an osteosarcoma readout for our Naxitamab and our DANYELZA products. So we're very, very excited about that. In addition, we are a commercial-stage self-funding biotech company. As of Q3, we have $87 million of cash and cash equivalents on hand and have financial run rate at our current program levels, as well as our planned program levels well into 2027, so very excited about that. We've reiterated guidance for 2023. We'll be reporting that formally and when we bring out our fourth quarter data, as well as providing '24 guidance at that time. As you see, we have a very significant pipeline, and we're really focused on bringing high-value products to the market and initiating with our partners, both in MSK as well as BCC initiated trials. And we continue to bring these forward in both Naxitamab and our SADA platforms. So our DANYELZA program, we've completed our 201 and our [ 12-30 ] and additional studies going on that will be initiated with our BCC partner. So Beat Childhood Cancer to bring it frontline in the high-risk neuroblastoma. In addition, we have our SADA platforms. Our 1001 study is initiated, and I've said we were in Phase I, completing Part A. I'll explain a little bit later about what that means. And we're also be initiating our 1201 later this year and first in-humans in the non-Hodgkin space for CD38. In the future, we also have 2 additional SADA molecules that we're further developing that we expect to have first in-human in 2025, and that includes both our HER2 as well as our B7H3. We'll also further advance and expect this year to initiate an IND for our GD2-SADA in neuroblastoma. So continuing our legacy in the neuroblastoma space in children, and that will be our pediatric trial with our GD2-SADA. So I think, now it's a good time as we discussed, to really turn our attention to what the SADA platform is and what that means to the future of the organization. So we're very excited about our novel platform of SADA. When we look at the radiopharmaceutical space, and I've spent the better part of 3 decades focused on radiopharmaceuticals in both diagnostics and therapies. We know there's challenges in reaching patient care. We know there's challenges in commercialization and infrastructure. Four of the big areas that we look at, one is infrastructure and manufacturing. We see the investment going in to make these pretargeted molecules. So to make a radioactive therapy, you need a specialized facility that can combine your protein or your ligand with your radioactive tracer. You have very limited time to make that delivery. So all of the investment going into that is specialized investment that just doesn't exist today. Physician participation has always been an issue. Most of the physicians that are actually treating and owning the patients can't prescribe radioactive products. They can refer the patient on to somebody who can. But in this case, the oncologist who has been treating the patient needs to refer them to another physician in order to treat. In participation, if you're not doing it yourself, it's not top of mind. So in this case, we have an opportunity to correct that as well. Administration sites. So from an infrastructure across the globe, we need specialized suites, radiotheranostics suites, lead line rooms, specialties bathrooms, specialized infusion centers in order to be able to administer all of the products that we currently have in the market, let alone what's coming. So we have an opportunity here as we discuss out at how we address some of those. And last is continuing drug shortages. And as you look at this and you're seeing a ramp up, it takes a while to build that infrastructure. So you see continuing drug shortages, delays in patient care as we're trying to get more and more radiopharmaceuticals to individuals and becomes much more challenging. So our goal is to simplify this process and to solve each one of these problems, and we can talk about what that means. So from an infrastructure point of view, as we start looking at this, we've got some opportunities with SADA. First and foremost, from a toxicity. The way SADA works is we actually inject a cold protein. So that protein is nonradioactive. It gives us the opportunity to get it into the system and to clear it out before the radioactivity comes in. So you'll remove the circulating drug prior to the radioactivity. So what's left is a [ painted ] tumor. so by doing that, you increase the dose to the tumor and decrease the toxicity to things like the kidneys as well as other salivary gland, lacrimal glands, bone marrow. The shortage is, when you look at that infrastructure, by injecting a cold protein first and then the radio tracer later, you no longer need these large facilities to essentially manufacture, release the product and ship it in such a short period of time in order to infuse it into the patient. In this case, you administer the cold protein in a regular infusion center, allowing the oncologist to participate in the infusion and treatment of their patients. Once that's infused, it's into the body, the PK levels you allow the drug that's circulating to exit the body and then send them to the nuclear medicine department or imaging centers for the injection of the radio tracer. That then allows you to utilize all of the existing structure in the infusion centers in oncologist offices, freestanding infusion centers, as well as outpatient centers for the cold infusion. And then, again, you're utilizing the nuclear medicine departments and licensed imaging centers for the isotope infusion. Any time you can utilize the existing infrastructure and get more physician participation with the patient, you're going to have more engagement and much better results as you look forward. The next thing, as you look at overall which isotopes can be used. I think it's important to understand there's a lot of excitement around things like lead-212, lutetium-177, actinium. We can be isotope agnostic. As we start moving forward and looking at the SADA molecule, since you're injecting the cold protein and painting the target and preparing it with open receptors to grab the isotope, you're then able to inject the isotope after the fact and choose which isotopes you want to use. So as long as we can create the linkers between the isotope and the SADA target that's already painted on the tumor, you have the ability to switch that out. So something like lead-212, where the time today is being burned in the manufacturing and release of the [ pretag ] conjugate, that's been done before the radioactivity is injected. Now you take the radioactivity and injected in the patient, and it tumor seeks based on the SADA molecule that's already attached to the tumor. So, as we look at these things from an infrastructure point of view on both manufacturing, as well as administration to patients, the ability to choose different isotopes in real time and decreasing toxicity levels to patients while increasing the targeted activity to the tumor, we feel as a recipe for success with the SADA platform as a targeted radiotherapy platform. One of the big things that from an investment point of view, if you look at that, you're no longer putting all of this investment in infrastructure out there in advance, in order to plan for the demand that's coming. We can utilize existing contract manufacturing or in-house manufacturing for the cold construct. So the SADA molecules that can sit on the shelf for 2 or 3 years is a nonradioactive substance and then utilize the existing radiopharmaceutical distribution network and isotope manufacturers to supply the isotopes directly to the hospitals and centers. The way our current structure is today with our clinical trials, we use a contract manufacturer for the cold protein, and we use isotope partners to deliver the isotope on a specific patients directly to the hospital. That's scalable and scalable with the current infrastructure that exists across the globe. As we look forward, what is SADA and why does it work? So SADA is a tetramer. And it's a tetramer that in this case, you have your anti-tumor component that's going to bind your tumor, as well as your anti-DOTA component that it will seek out the DOTA that's circulating attached to lutetium. So it allows us then to have this tetramer attached to the tumor while it's cold. What doesn't get attached to the tumors breaks up into 4 monomers and is easily excreted through the kidneys. So what we see, and I'll show you a little bit of what the PK curves look like and the elimination of the circulating tumor, meaning not only is it binding to the tumor, it's also being eliminated renally before the isotope injection. And then there becomes a window in which you can inject the isotope to maximize the effect of the drug. Just as a little bit of [ why ]. How is this technology? And why is it important? If you look at this from an IgG or even from looking at injecting a pretag conjugate, you're going to have an issue where you've got circulating drug and radioactivity in the system sinking out the tumor that's irradiating other things. In this case, you see the diffused radioactivity within the animal model here. As a SADA in injecting it and you look at the curves, you allow the SADA to tag prior to the radioactive injection, as the blood levels of SADA drop and it becomes attached to the tumor, then you inject the radioactivity, what you'll see is focal uptake in the tumor. So if an animal model, you're looking at this and saying, this is ideal for patients. Can it be replicated? Our answer to that is yes, and I'll show you a few slides as we go forward. But ideally, what you want to do is maximize uptake in the tumors, because dose matters. And we've seen that with other studies, less dose, less effectiveness. We want to make sure we're maximizing the effectiveness within the tumor. Where are we today? So we're in humans with SADA. So we validated that the SADA molecule, the SADA platform works, that we can do an in vivo tag within a human and inject it. So in Part A, we've got a study design of 15 to 18 patients. This is a safety study. It's not an efficacy study. But the nice part about radiopharmaceuticals, you can watch the drug work. We've got a secondary gamma that comes off the lutetium that we're able to image with the gamma camera. So what we've done in this first segment, this is a dose escalation study of trying to understand what the right level of protein, called [ proteinase ] to inject. So we've already completed the first 3 cohorts and moving on to the fourth cohort this month. With that, we looked at 0.3 mg/kg, 1 mg/kg, cohort 4 were moving to 3 mg/kg and then we'll be moving to 10 mg/kg. That's Part A of the study. We're also looking at that window. How much time does it take to clear out the circulating GD2-SADA molecule prior to injecting the radioisotope. The window that we're focusing on is 2 to 5 days. So with that, our goal coming out of Part A this year is to have a specific protein load that we'll be looking at for the second Part B of the study, as well as narrowing the window for maximal opportunity to treat the patient. Having a wide window is very nice. So what we're looking at is, where is the starting point of injection and where is the last point in which you can inject. Having a window wide enough allows for logistics and delivery of the isotope without running the risk of missing the optimal time of injection. We'll report this out at a medical meeting later this year in totality and what Part A looks like, but I'll give you a little bit of preview with those first couple of patients look like. In Part B, we'll be escalating the dose. I said dose matters. So with this, we're focusing on increasing the dose from what you see today that's approved in the market is all standard 200 mCi, right, 200 mCi per dose. For us, we want to scale this up as high as 750 mCi, understanding we're seeing less toxicity in the kidney's less retention. So if you don't have the toxicity, let's deliver the highest dose possible over the longest period of time to get the best results. So part of this will be scaling up to see how much we can give, while limiting the toxicity. And then Part C, we'll get into the times when we start doing the repeat dosing and start seeing more of the conventional therapy that you do today to start getting the efficacy signals. So these are designed as safety studies and eventually getting to the point where we could see some efficacy. This is where it gets exciting, right? So I look at this and this is where I get very excited about SADA. This tells me -- this is the first patient that tells me that the SADA platform is validated to work. So what we have here is an Osteosarcoma patient. With this patient, they received the lowest protein dose in the study, which was 0.3 mg/kg. At 48 hours post protein injection, we injected 30 mCi of lutetium DOTA, which the patient received and 24 hours after that dose, we did this spec scan on the patient to see where the GD2-SADA went. In this case, we see a very, very focal uptake of the osteosarcoma tumor and very little uptake in the healthy tissue outside of the tumor. So what this tells us is yes, you can inject a pretargeted nonradioactive SADA molecule that will then grab the circulating lutetium and concentrate in the tumor. But this is an [indiscernible], right? So you want to get excited, but not so excited that you sell the house. As we move on to the next one, this was the next patient. Four lesions were identified on CT scan, another osteosarcoma patient with GD2-expressing tumors. This patient, again, received the smallest protein load at 0.3 mg/kg, 48-hour lag time and an injection of 200 mCi of lutetium DOTA. With that, 24 hours later, we did the spec CT image on the patient to validate that it was targeting those tumors. If you look at this, there's a direct relationship where all 4 tumors were painted, all 4 tumors concentrated, the GD2-SADA lutetium into the tumors with very minimal uptake elsewhere. So in the first 24 hours, massive clearance outside of the tumors. This again tells us that the SADA platform is working and that the GD2 is targeting the GD2 expression on these tumors. This is where I start getting excited and how it starts going on the market. So why does it work? Why does it get that pre-targeting? So these are some of the first few patients that we took the PK data on. This is the blue line is 0.3 mg/kg, while the purple line is at 1 mg/kg. So we saw that initial blood circulating load of the GD2-SADA and then we see the rapid clearance from the blood. The reason we're using that 2 to 5-day window is, as you can see, both the 0.3 mg is the one. The majority of it has exited the circulating system by the 48-hour point and start going into more of an equilibrium. So at that point, we're looking at being the front end, where you're getting very minimal toxicity and then continuing out to 5 days to see where the book end is of that where you want to cut off the window for doing the injection. So this upfront has given us a lot of direction on what that potential window can look like. So we'll be initiating our 1201. So this clinical trial is approved by the FDA to start. We're recruiting sites as we speak. We'll go first in patient. We design it in a very similar way by design, because not only do we want to validate CD38, we want to validate the process in which we qualify these products in order to get them into patients and into the market. So, part of looking at SADA as an entire platform in a factory for producing targets in the targeted radiotherapy space by developing these clinical trials in a very similar way, we'll be able to compare the results of each trial and start to get some data that compares each product as a platform and potentially creates an opportunity for us to generate the next products in a much more faster development in a quicker point. But it will be a Part A of the dose escalation. Part B will be isotope and Part C will be repeating the 6 cycles. And just to close out on this, we're extremely pleased with how the SADA platform is progressing. What this means. We've got our GD2 trial, our 1001 study that we will be reporting out at the end of this year, be initiating our CD38 trial. We've got 2 additional SADA targets in development heading for '25, which is the HER2 and the B7H3 and again, advancing GD2 and starting that in our pediatric neuroblastoma trial as well. So, we've got a very much a significant potential to shift the paradigm, get additional physician participation and utilize the existing infrastructure to solve much of the challenges that occur today in the radiopharmaceutical space. So we're very excited about that. So we'll talk a little bit about the commercial of company. So, this was a little bit more forward-looking on where the company is going, but what's fueling it, right? Who are we as a company? We've talked about how excited we are about DANYELZA and what it's doing for patients, but also what it's doing for the organization, allow us to be that self-funding biotech. So a few areas. We've got the humanized antibody for relapsed and refractory high-risk neuroblastomas and we're the only one in the market with that. Also, it has some strategic advantages of some of the other anti-GD2s. So we've got outpatient setting. We've got rapid infusion, and we've got minimal toxicities associated with the product. So right now, as we look at the addressable second line in the neuroblastoma market, these are small markets, but it's a high value, low volume market that treats an unmet need. For neuroblastoma, it's in children, in infants, it's the most common cancer in infants. It's heartbreaking. And for us, there was a personal mission in why it's named DANYELZA, who [ are ] treated and how it came to market. And it's definitely something we're taking the time to look at if you have some time later. But at the end of the day, we have the ability to treat these patients in ways that they haven't been treated before in order to extend their lives and put them in a much better place. We continue to launch the product, continue to grow it forward. Q3 reported sales of $20 million. So that's 2 years post launch. And we also are continuing to move this earlier and earlier. We launched initially with the majority of the patients being late line or third line. We've moved up to second line with plans to do some additional studies in partnership with the Beat Childhood Cancer to move into first-line induction in neuroblastomas. We've got -- we added 7 sites on just this quarter. So we've moved to 52 [ trading ] -- from 52 trading sites to 59, which in this space is fantastic. We continue to grow that, as well as the number of practitioners actually prescribing. We have a large ex-US. So we've launched in China. We're continuing to grow that. We've gotten 2 approvals in Latin America and will be launching early this year in 2 additional countries. We've got European coverage on a named patient basis that we provide through the web program. So we're very excited about this. And this continues to be a driver of who we are and what we are and we've treated 167 patients to date, which is just in this space is absolutely fantastic. So we're increasing the share. We're up to 17% of the anti-GD2 market and continuing to grow that overall. This slide is extremely important. This, when you look at it is around Curie scoring. The Curie scoring has to do with the bone and bone marrow involvement in neuroendocrine tumors. So by lowering the Curie score, you have better outcomes. In this case, looking at what DANYELZA has done, we've seen a reduction or stabilization in bone disease and 46 of the 48 patients that were treated. So, I won't speak a lot to this, but at the end of the day, this really shows you how DANYELZA is taking bone disease, stabilizing it and reducing the Curie scoring for better outcomes. So it's very exciting for us as we go forward. As we look forward, we've got some additional trials that we're working on. We expect to see the initiation of the Beat Childhood Cancer in first line. We'll be supporting that trial as well as providing DANYELZA for the trial. In addition, we've got additional expansion with Memorial Sloan Kettering, who will have a readout in the second half of this year, probably fourth quarter. That trial is closed, and that was in around osteosarcoma, [ with ] GD2 or anti-GD2 can do for that. And then our Ohio State University Comprehensive Care and that was target enrollment of 42 patients. So we're continuing to advance DANYELZA, look for additional opportunities to grow the product and reach more patients. Overall, this is a look at both the drug studies in play, as well as the additional indications being looked at in areas of interest. So really, a focus -- we're in high-risk neuroblastoma, looking at bringing it forward earlier in the care looking at osteosarcoma, soft tissue sarcomas, breast cancer as well as melanoma. DANYELZA reaches a significant unmet need. So for us, we're going to continue to invest in that. We've got our studies that are moving forward. We've got our grants, we're continuing the commercialization in high-risk neuroblastoma and as well as looking at potential multi-potential advantages over our competitors and what's out there today. So, being able to infuse this in the outpatient setting, rapid infusion, minimal toxicity, makes DANYELZA and it should be the drug of choice in the space. So a few takeaways as we come to the end. We've talked about our novel platforms, both in the monoclonal antibodies, as well as our SADA platform. We're very excited about that and excited about what the future means. We've got our commercial leverage of a growing DANYELZA product that allows us to go ahead and continue to fund our R&D on a net positive basis. We've got our milestones coming this year that are going to be important as we move forward as a company and start to advance both of these. And then again, we've talked about our financial independence and a runway well into '27. But as we bring these products to market, we have the opportunity to accelerate some of the R&D, as we validate these platforms, to validate the targets and work with our partners to bring products to market. So let me close by saying, I'm very excited about where Y-mAbs is today, what we're doing for patients, but more importantly, what we can do for more patients in the future. Thank you, very much.

Thank you, Mike. It was a very informative presentation and congratulations on all that your team has achieved in the past year.

Thank you.

We will now open up for Q&A. If there is no Q&A, we can close out the session. Thank you so much for attending this presentation, and thank you all for joining us here.

Thank you all.