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

Good afternoon and welcome back to the 43rd Annual JPMorgan Healthcare Conference. I'm Sean Perkins, an associate in the Healthcare Investment Banking Group, and I'm joined today by Y-mAbs. I'm very pleased to introduce Mike Rossi. And with that, I'll not waste no further time and hand over. Thank you very much, Mike.

Well, thank you, and thank you for joining us today for the presentation of Y-mAbs Therapeutics. I'm Mike Rossi, I'm President and CEO, and I'm proud to serve Y-mAbs and our patients, both in the U.S. and globally. So I'm excited to take you through our company's presentation and excited to share updates for our business. And where we are, where we're heading, and more importantly, who we are doing that for. So just a quick note on our disclaimer. These are forward-looking projections. You can find these on our website, on our SEC filings as well as our most recent press releases. So as we look at Y-mAbs, our mission and reason we exist was really to build and deliver novel therapeutics to patients as quickly as possible. We are able to do this and deliver this through our DANYELZA product that focuses in the pediatric oncology space for neuroblastoma. We're also working very diligently to do the same for our radiopharmaceutical platform. And we're excited as we move forward to develop this and really focus on benefiting patients and their families with the treatments that we provide. So looking overall at the Y-mAbs business, there's really -- our major areas of focus. We have next-generation novel platforms that are focused in monoclonal antibodies as well as our novel self-assembly and disassembly pretargeted radioimmunotherapy platform. So novel antibodies are focused on our DANYELZA product, which is an anti-GD2 product. And our self-assembly disassembly platform allows us to develop multiple radiopharmaceuticals based on the novel 2-step approach. We also have enhanced commercial capability. So we're in the unique position of being a revenue-generating biotech and allow us to take our revenue that we're generating from DANYELZA and reinvested into our platform. We've got a U.S. commercial footprint that allows us to directly service patients and customers in the U.S. with partnerships ex U.S. through our distribution partners to expand in multiple locations around the globe. We provide these products through approvals in several countries as well as on patient name basis in areas where we don't have approval. We've got a deep bench of industry leadership, and we continue to grow that in the radiopharmaceutical business. So I've spent the last 30-plus years in developing, manufacturing and distributing radiopharmaceuticals, both in diagnostics and therapeutics. We were fortunate enough, in a very competitive industry to bring in some top leaders within this industry to focus on development of our radiopharmaceutical platform. If you look at our broad pipeline potential of our radiopharmaceutical platform, it allows us to deliver multiple targets and treat multiple cancers using the same overall platform. So we're able to leverage the efficiency of that to deliver on multiple cancer types. Let's talk a little bit about our achievements. So 2024 was a big year for Y-mAbs in both execution and realignment. So DANYELZA remains a very important therapy in the high-risk relapsed/refractory neuroblastoma space. We had one of our partner sites, Memorial Sloan Kettering in New York, presented, DANYELZA osteosarcoma data at CTOS in November, looking at using our anti-GD2 therapy for the treatment of osteosarcoma. We also increased our DANYELZA wild demand in ex U.S. markets, including approvals in China, Brazil and Mexico and then named patient programs in Europe and Turkey. Our SADA PRIT advancement keeps moving forward. We've shown proof of concept with our SADA PRIT platform to achieve our GD2 SADA Phase I trial. We have two ongoing trials. One is focused in GD2 similar to DANYELZA. And with that trial, and we'll talk about it a little bit more later, is a basket trial looking at multiple indications that are potentially GD2-expressing including sarcomas, melanoma, small cell lung as well as adult neuroblastoma. We've also activated four sites for our 1201 trial, which is a CD38-based trial, and that is targeting non-Hodgkin's lymphoma, so refractory cases of that. And for us, it was important to look at these to validate both solid tumors and circulating tumors to develop our -- to dose with systemic radiotherapy. We know many of these hematologic tumors are radio sensitive, and it's very difficult to do that with external beam radiation as difficult to hit a moving target. In the case of systemic radiotherapy, we're able to target the receptors on the cells and deliver radiotherapy where it exists. Financially, we showed our -- we gave some preliminary results on Friday in our press release that showed unaudited revenue, net revenue of $88 million. And again, we'll provide the final revenue on that when we provide 2024 date at the -- in March of Q1, and we'll also give '25 guidance at that point in time. Our business has been extremely capital efficient. So we're able to utilize the revenue and cash flow from DANYELZA to fund our ongoing operations. So we've had very minimal cash burn in the organization, and it's allowed us to really reinvest in the company and develop our radiopharmaceutical pipeline. So overall, one of the announcements we made on Friday was aligning Y-mAbs into two business units -- and two distinct business units: one being at DANYELZA commercial business unit. As we've advanced that product into the commercial stage in life cycle management, it was important for us to optimize and maximize that. And the second is to move into a radiopharmaceutical franchise. And the radiopharmaceutical franchise is in the R&D space and really a development franchise without the commercial needs at this point. So in order to optimize both and to bring in the right talent to drive these forward and move it forward, we saw this as a great opportunity. One of our main goals in our radiopharmaceutical is to continue to expand our domain knowledge and our internal capabilities of both people and process to advance our products much more quickly. The other areas accelerate execution in both our commercial and R&D. So we want to continue to expand DANYELZA and make it available to more and more patients in the U.S. as well as ex-U.S., but more importantly, with our pipeline is to create data, validate our targets platform and move into sharing data with our medical colleagues as well as our investors in a much more timely basis. With that, it's focused on best utilizing our capital to invest in the business and to grow it. So we've been very capital efficient. This past year, unaudited, we had $11 million in cash burn. With that, we have, again, preliminary data of $67 million on the books at the end of the year, which allows us a runway well into '27. So we continue to optimize our cash utilization to invest in the life cycle management of DANYELZA and the development of our radiopharmaceutical platform. Also, it's important to align our strategy and budget. So we know we have limited cash to invest, and we want to make sure we're putting it in the right areas of the organization. With that, two separate business units allows us to do that. So deploy the cash, to advance DANYELZA, both U.S. and ex-U.S., while we continue to advance our radioimmunotherapy platform. And with that, we'll actually get to our radioimmunotherapy platform. This is an exciting and innovative platform that is game-changing for radiopharmaceuticals. Radiopharmaceuticals have been a very interesting and hot topic over the last few years as we see more and more products coming to market. But we also know there's challenges. With those challenges, there's challenges in infrastructure and manufacturing, radiopharmaceuticals are not easy to make. They also have very short half-life and it's a just-in-time manufacturing process. So it's important to look at the challenges associated with continuing to grow that. And what that means as a manufacturer, as a company and more importantly in how we treat patients. The second thing that we really look at as a challenge within this space is physician participation. Physicians like to treat their patients. They want to be hands-on with their patients. There's an intimate relationship between oncologists and their patients, and how they treat them, and how they want to continue to do that. Radiopharmaceuticals are a bit different in that. Most physicians that are actually have that relationship with the patients can't treat them. They need to refer them to a nuclear medicine physician that has a radioactive materials license. That's an authorized user of radioactive materials to actually administer these targeted radiotherapies. In our case, we have a solution for that, and we have a way for physicians, both nuclear medicine as well as oncologists, urologists, endocrinologists to participate. Administration sites are another issue. As you look at the number of radiopharmaceuticals being developed and understanding that there are a limited number of sites that can actually treat patients and a limited number of physicians that have these -- the training and the authorized user status to do that. We need to better utilize our existing infrastructure to treat all of the patients that we can across multiple companies and the products that are being developed. And finally, it's continued drug shortages. We see issues, weather our issues. When you have a product that has a 24- to 48-hour expiration after it's made and it has to be transported across the country or across the globe, it becomes very challenging to reach these patients. There's also with the scheduling a limited number of slots to manufacture them. We saw this happen in the prostate space with the release of some of the new prostate products where patients are challenged to get treated. So we look at this platform as a way to overcome that. And how do we do that? So as we look at the SADA platform, first and foremost, from an infrastructure point of view, we don't need a facility to assemble the isotope to the drug. So most radiopharmaceuticals today, actually all radiopharmaceuticals today are pre-tagged radio conjugates. So meaning you manufacture them as a radioactive drug the very short half-life and a very short expiration, ship it and it is injected into the patient as a conjugated radioisotope. In our case, we separate the two, which allows much more efficiency in not only distributing the isotope, but a much lower cost of goods because we don't need the CapEx or the OpEx to have a facility to assemble them because that actually happens in the patient. It's an in vivo tag radiotherapeutic. The other thing we talked about was physician participation. We could leverage the infrastructure within oncologist practices in an infusion center that doesn't have a radioactive material license to actually administer the SADA drug. There's a delay between the time you administer the drug, which is anywhere from 2 to 3 days. The patient then goes to a nuclear medicine department or an outpatient imaging center for the injection of the isotope, which then binds to the tumor based on the SADA that was injected upfront. The other opportunity with this is to use much shorter half-life isotopes. So we -- there's a lot of industry talk about actinium, which has a longer half-life. But as we get into things like Lead 212, which has a 10-hour half-life or Astetine, which is even shorter, it's very difficult to find a commercial path forward to be able to take a very short-lived isotope attach it to a ligand or a drug, clear all of the release requirements required under Part 211 on a therapeutic and get it to the patient before it disappears. So if it takes 48 hours to manufacture and release a product and it's lead 212 with a 10-hour half-life, you've lost 97% of your radio activity before you're able to release that from injection. So it's just not a viable path forward. In our case, you're able to assemble it in the patient. So it's a much faster release criteria to conjugate that in the patient. So a lot of opportunity to be very specific on what those isotopes look like in broader use within the patients and more importantly, more specific tumor attachment. So how does it work? And what is the 2-step approach. So as we look at the SADA 2-step, the drug itself for the SADA has four monomers assembled into a tetramer. And why is that important? One of the things that you've seen, full antibodies have a long circulating half-life. We've had some great success in the past, tagging full antibodies, but you also have a lot of toxicity associated with that because it circulates for a long time within the body. In our step, what we do is we assemble four monomers at a central point with a linker into a tetramer that is the size of an artificial antibody, creating a longer circulating half-life, but this drug is nonradioactive. And what this is doing is pretargeting the tumor with two binding sites, 1 binding site that's tumor specific. In the case of our 1001 trial, it's GD2. In the case of our 1201, it's CD38. And we changed out that particular tumor-specific linker on the monomer so that it is targeting the tumor that you're looking for. The second binding site on each of these monomers is an antidote binding site. This is where the isotope is going to collect. This is the velcro between the isotope and the tumor. These 4 monomers are assembled in the tetramer with a longer circulating half-life allows time to get on to the tumor and paint it or pre-target it. And over time, it begins to disassemble. The disassembled tetramer into the four monomers are 60 to 70 kilodaltons, which allows it to be renally eliminate it rather quickly. And for us, one of the important things, and I'll speak to this in the PK is waiting for it to clear the blood. So what's different with the radiopharmaceuticals as you wait for the nature of the drug to clear out of the blood, so the only available binding sites left are painted on the tumor. So you get a much more efficient tag of the isotope to the tumor, much more rapid clearance of the non-bound radio activity, which is delivered in the second step. And that allows you to then treat more patients with higher target background ratios. So just to give you a quick update on where we are. So we have two programs that are active -- two clinical programs that are active in our radiopharmaceutical pipeline. The first is our 1001 trial. We dosed 21 patients to date, and we will be reporting that data from our first 6 cohorts in the second quarter, but we did give a preview. So what we anticipate to see in this data from our ongoing 1001 trial, in the 6 sites that are active is the dosing interval between the protein and the isotope, also looking at the PK dosimetry, rates of excretion, concentration in tissues, tumor burden as well as the PET CT scans. And we'll show those in how the tumors light up, how these pretargeted in vivo tag radiotherapeutics will work. One thing we're still looking for is what is the optimal and safe protein dose so that we have the maximum load onto the tumor and also the most rapid clearance out of the blood to get to the isotope as quickly as possible. So we continue to learn a lot from our 1001 trial, as this is the first time the platform was administered in humans and also the first time in vivo tag radio therapeutic enter this space. So a lot of valuable learnings that we'll be taking forward to derisk our platform moving forward as we move into higher valued targets in the very near future. So of the 21 patients we dosed, what's unique about GD2 is there's no IHC. There's no way to tell if they're GD2-expressing tumor or not. As much experience as we have in the anti-GD2 space with DANYELZA that's administered to all pediatric patients with neuroblastoma because we know that's a high rate of GD2 expression in neuroblastoma. As we move into other indications like the sarcomas, melanoma, small cell lung, there's no way to predetermine whether the patient's GD2 expressing or not. So this showed validation in the 2-step approach that we can do an in vivo tag therapeutic that it will show uptake and nine of the patients -- nine of the 21 have shown GD2 expression and uptake in the tumors. We'll go through those more in depth. But you can see at the bottom, we had 11 sarcoma patients. Of those, five of them show GD2 expression and uptake. Melanoma, four of the eight patients showed uptake, then we had one small cell lung cancer and one adult neuroblastoma patient that neither showed uptake, not surprising in a patient like this adult neuroblastoma patient, which is an ultrarare disease was heavily pretreated with the anti-GD2 therapy and generally creates a degraded receptor, so you wouldn't necessarily expect to see the uptake. Just looking at the scan. So this was one of our -- this was our first patient that showed uptake. This patient received the lowest safety dose that we were providing as we were scaling up the dosing was 0.3 milligram per kilogram. 2 days after that dose, we administered 200 millicuries of [ DOTA cage ] lutetium and 24 hours post the isotope, we did these spec CT scans. So at the top of the picture you'll see for each of the tumors, what the CT look like and what the functional image of the lutetium look like. So lutetium gives us a secondary gamma that allows us to image it with a nuclear medicine camera. And these five tumors all in the same patient are very definitive that we can do an in vivo tag therapeutic and show what GD2 expression looks like as well as treat it. We'll be moving forward with the diagnostic therapeutic combinations, which will then allow us to not only diagnose and stage but to treat and then monitor progression. So great opportunity here in nuclear medicine to have that theranostics approach using the same drug with both a pedometer as well as an alpha or a beta emitter to treat. So looking at some of the PK levels. And again, in traditional drug development, you're looking for high PKs, you're looking for the higher end of the curve, what does that look like from a therapeutic perspective. In radiopharmaceuticals, what we're looking for from the drug is not necessarily for the drug to cause a physiologic change or the pharmacology from the drug to do that. The drug is the carrier or the binding site to deliver the radioactive material. In our case, what we're looking to do is saturate the tumor, but to clear the majority of it out of the blood prior to injecting the radioisotope. So what this shows is as we scale up and easiest to look at on the right-hand side, but the lowest line is 0.3 milligram per kilogram. When injecting in the patient, the peak activity is actually where you can begin to inject. So we wanted to make sure that we saturate the tumor as much as possible and inject it at the right point. So for us, it's a 1,000 nanograms per ml is our threshold to inject the isotype below. And that is right about where the 0.3 milligram per kilogram would start out. And the 1 milligram per kilogram in saturating the tumor takes about 36 hours to drop below that 1,000 nanograms per ml, which is ideally where we're injecting. So that's going to be in the, call it, the 2-day range and moving forward. As we triple that and moved up to 3-milligram per kilogram, we saw much longer clearance time which was going out more to 4 days before it crossed that milligram per kilogram threshold. Why that's important is -- we're determining right now how much is enough to paint the tumor and get us to the point where we can inject the radioactive material as quickly as possible to make sure we're getting the highest absorbed dose to the tumor. So the clearance rates were similar, but it allowed us at a little bit lower dose to get to the isotope much more quickly. What's going to be different? So what did we learn, and how we're moving forward. So GD2, people ask, why GD2, right? We had a lot of experience with GD2 from our DANYELZA product. We were able to take a fragment of that attach it to our SADA complex and get into humans very, very quickly. So from the time we in-license to the product until the time we had the drug in clinical use in humans was under 2 years, which is remarkably fast for our product. Challenges with GD2 is, you can't see the expression upfront. So you don't know until you inject it. So this was the first product that was really able to image those GD2 receptors. So the second part of this is the 1001 trial is a safety trial. It's not an efficacy trial. It's a validating trial to show that, a, you have a safe molecule and b, that it does tag the tumor and get into the tumor at a concentration, which you can see it. Optimization work needs to be done on that. So we used the naked DOTA, which is a very simple, safe conjugate or a linker in order to deliver the lutetium to the receptors. Our next step is to optimize that. We have proprietary linkers and chelators in development. that we've been working on simultaneously that will increase the affinity to the tumor as well as the residence time on the tumor. That's the optimization work that's going on right now, along with looking at the specific activity of the lutetium itself, to make sure we have enough particles of lutetium to saturate all four of those binding sites on the tetramer delivering the highest dose to the tumor as possible. So there's still more work to be done on that, but it is giving us a path forward to derisk the platform and optimize what is injected in the patient. So there will be some changes to the trial moving forward as we work through the optimization and work through what the right path forward is on the linker and chelator. So let's turn to our 1201 study. So this is an active study. It is a CD38 based study design, very similar to our 1001 trial, but focused on non-refractory non-Hodgkin's lymphoma. Why CD38? We were able to take some knowledge from our team in Denmark that came out of Genmab and were part of the CD38 development of their full antibody. We're able to utilize some of that sequence to get into humans to validate this and circulating tumors. So right now, we've cleared four sites. There are six sites selected as well, and we're searching for that first non-Hodgkin's patient to treat. So active site, we expect to dose the first patient this quarter, and we're very excited to do that. So talk about our pipeline. So what's next in radiopharmaceuticals. We went through an exhaustive process over the last 6 months of starting with over 1,200 targets, that are known in the literature, both really focused in oncology, but also some targets with some dual use outside of oncology. We were then able to narrow those down to 20 to 30 cancer types, bring it down to the next level of refinement and looking at targets of interest that would be commercially viable, exciting for us, areas of unmet need, and then get into an assessment framework of prioritizing those. So of the over 1,200 targets, we prioritize between 40 and 50 targets to put into our pipeline and look at over the next 3-plus years. and move into preclinic and clinical development. So we'll be prioritizing those and that will be part of our 2Q update on what the radiopharmaceutical pathway looks like moving forward. So we're excited to provide that update in Q2 and more importantly, focus on what that means. So as we look at these targets, there's going to be three main areas of focus or 3 franchises within our business that these targets flow into that we're interested in commercializing There'll be some additional targets that don't fit our franchise model, that will be good BD opportunities for other pharma companies that would fit their franchises. So for us, we're excited about this platform. This platform can produce a lot of drugs in a very short period of time. We're excited about that. And for us, at Y-mAbs, it's about focusing in three main areas. We'll disclose what they are and what our new targets are in the second quarter. But we're very excited about that and what these targets are. There'll also be a variation of the targets and what we're going for. So we're looking for a good fit and good validation in some of these targets. Other targets will be novel targets that are very high-value targets. We'll also have a high-risk, high-reward targets, and then we'll have some validated targets in this space. So people understand what both this means and why there's such an advantage to using a pretargeting platform. So moving out of our radiopharmaceutical and into our commercial business and just a quick commercial update on DANYELZA. So we've got multiple potential advantages of DANYELZA in the GD2 space, and it's with this targeting antibody. It's modest toxicity, it's shorter infusion time, the ability to be administered in the outpatient setting as well as meeting a significant unmet need in a critical patient population. Neuroblastoma, for those of you who know it or don't know it, is the most common cancer in infants. Although it is a rare disease, it is the most common cancer in infants, and it's debilitating. So for us, we're focused on the high-risk relapsed/refractory space, which is 40% of all neuroblastomas. DANYELZA has also the unique indication of being indicated for bone and bone marrow involvement, which allows us to really help patients that have progressed into that high-risk category. So just a couple of takeaways on this and what we're looking at. So some anticipated milestones in 2025. We've got our ongoing GD2 trial, or 1001. So we'll do that Part A update in the second quarter. We'll also show the optimization data, as we talked about, optimizing the chelators and linkers. And then we'll update on what's next. So what's the Part B and what are we moving into with our 1001 trial. 1201 talked about looking for that first patient. So we'll announce as soon as that first station is dosed in our ongoing 1201 trial. And again, we talked about the new high-value SADA Prit targets in the upcoming pipeline and what that will look like for our strategy and path forward on that. We also anticipate a new ex U.S. marketing approval for DANYELZA. We are also looking at high-value opportunities to expand the DANYELZA labeling into osteosarcoma based on the data that was received from the MSK trial that they conducted. And we will provide at the end of the first quarter, our fiscal year '25 guidance as well as our full audited 2024 earnings report, and that will happen in March of '25. So just back to who we are as a business, and why it's important. I'm very proud to lead our Y-mAbs Therapeutics team and the work that we're doing both in pediatric neuroblastoma as well as our radiopharmaceutical pipeline and development. we're very excited to continue to move that forward. So I'd welcome any questions from the audience or any questions online at this point in time.

Thanks very much, Mike, and we'll open the floor to questions now. This is being live streamed. So we just ask that you give your questions to the microphone so that it can be heard. That's the sign of a very good presentation, but I think we have a question here.

So with DANYELZA, do you see caregiver led or patient-led discontinuation before kind of the disease returns. Do you see -- what I mean is that for DANYELZA, do you see the caregiver or the patient discontinuing treatment right, before say lapse or kind of it. So what I mean is that are the nonmedical reasons why they decide to discontinue treatment given that it's a terminal patient.

Yes. So DANYELZA -- the way DANYELZA works is you do multiple cycles of the product until you see a complete remission. So what we do on those patients is as they move into complete remission, some patients will continue to get some doses beyond that in order to keep them in remission. There's also an inhibitor that can be used an oral inhibitor that was approved last year that could potentially maintain duration of response, but there's the opportunity to go back and treat again. So DANYELZA is a product that a lot of these patients, and we saw it with -- the patient I mentioned in the 1001 trial that came in as an adult neuroblastoma patient had multiple cycles of the anti-GD2 therapy. So these are products -- your hope is to go through and get through four, five, six cycles, put them into remission and keep them there. If you need to go in and treat again to get them back in remission, you do that. But really, the goal with DANYELZA is to clear the disease. And that's why it's important to have that bone and bone marrow indication because if you don't clear it from the bone and bone marrow, it will come back. So that's one of the advantages of really making sure that you get into complete remission, you get through all of your cycles and you clear the bone marrow and then have much better outcomes.

Thank you very much.