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

Okay. We'll go ahead and get started. So welcome, everybody, to the Wednesday afternoon session of the 2020 JPMorgan Health Care Conference. My name's Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Tessa Romero and Matt Bannon from the team. Our next presenting company is Y-mAbs Therapeutics, and presenting on behalf of the company, we have CEO, Claus Møller. Claus?

Thank you very much, Anupam, and thank you, everybody, for coming and listening to Y-mAbs' presentation. Let's jump right into it. Our mission is to become the world leader in developing better and safer antibody-based pediatric oncology products addressing key unmet medical needs. We have a lot of passion behind this company. Our Chairman, Thomas Gad, had the unfortunate experience to have a daughter that went through the treatment with both our lead compound. Fortunately, she's doing perfectly fine today, but that inspired him to start Y-mAbs, and we started the company about 5 years ago. August 2015, we licensed in the 2 lead assets from MSK, including some technology platforms under which we're developing additional bispecific antibodies and other great stuff. So we are in a situation today where we have 2 pivotal stage candidates: Naxitamab is a humanized naked antibody; and omburtamab, that's an antibody that we put radioactive iodine on. Both of them have breakthrough designation from the U.S. FDA. They also have orphan drug designation and rare pediatric disease designation. We started a rolling BLA submission for naxitamab in November 2019, and we expect to complete this rolling BLA before the end of first quarter. We also expect to complete a BLA for omburtamab before the end of first quarter this year. We have an upcoming pre-BLA meeting with the FDA here in February, and shortly after that, we should be ready to put together the rest of the BLA filing and put it into the FDA by the end of first quarter. We have a potential to expand our first 2 antibodies and their first indications into additional indication and additional lines of therapies. We have several studies ongoing to secure this. And also, last year, in February, we put our first bispecific antibody into a Phase I/II dose escalation study. And the great thing is today that 11 months later, we are still standing here. We don't have a clinical hold which means that it has been safely dose-escalated 6 times for now. And I'm going to give a short update on the status for that also. In addition to this, we have a GD2-GD3 Vaccine that we use for kids after they have come into remission to try to induce endogenous production of antibodies against GD2 and GD3 to prevent them from relapsing when dormant stem cells from the cancer starts dividing. And then we have a very nice financial situation after doing a secondary offering in the end of October last year, securing our financing through the end of 2022. So we have 5 programs, as I said, naxitamab and omburtamab, the 2 lead programs that are going in for BLA submissions this quarter. We have the GD2-GD3 Vaccine. We have the first bispecific antibody, and we have omburtamab-DTPA conjugated antibody that can chelate lutetium-177, which will be our second-generation radio-conjugated antibody. Behind these programs, we have a number of additional bispecific antibody constructs that we are working on. We have also disclosed that we expect by fourth quarter this year to start an IND for a CD3 -- CD33/CD3-bispecific antibody with the intention of treating pediatric AML with that antibody. Obviously, if it works great in pediatric patients with AML, it's potentially also very valuable for adults with AML. The markets that we are addressing with naxitamab, potentially in our second line first indication could be about 300 patients per year. Advancing this into frontline, where we right now have 2 single-center Phase I studies ongoing and plan to start a multi-center study later this year could be another 500 patients. And we also have an osteosarcoma program for this antibody, totally addressing potentially up to 1,000 patients. For omburtamab, the first indication is 80 to 100 patients a year in the U.S. We already have presented data last year at ASCO for 39 patients with diffuse intrinsic pontine glioma showing very promising indications of efficacy in this fatal disease also. Nobody survives a DIPG. 5-year survival is less than 1%. And we have treated 39 patients. We still have 7 patients alive, and we have 1 patient that is more than 5 years out now and several patients more than 3 years out. We're also using this antibody in DSRCT, a very rare peritoneal cancer where we put the antibody IP. Potentially at least a 500-patient population addressed with this antibody. Naxitamab, our lead humanized antibody against GD2, we have previously shown data for primary and secondary refractory patients, and we had updates on these at the SIOP conference in September last year. And what we have seen is in primary refractory patients, we get about 70% to 80% response rate with a 50% progression-free survival at 2 years. In secondary refractory patients, which means it's patients that have been in remission after frontline treatment, then they relapse, then they get salvage chemotherapy and they are resistant to salvage chemotherapy and then we treat them with our antibody, and we can still make 37% of these just on naked antibody go into remission. If they do not come into remission on that, we put them on what we call HITS, which is a humanized antibody naxitamab, irinotecan, temozolomide and sargramostim. And we can put another, about approximately 40% into remission of those. 36%, 2-year progression-free survival shows you that it's really meaningful remissions that we see in these patients when we put them into remission. For the multi-center study, the FDA gave us as a task to do before they would let us file for approval. We have presented data -- or not presented data, but we have disclosed data from the 24 patients that goes into the filing where we have more than 70%, as we said, of response rate among the 24 patients. Now originally, when we talked to the FDA and they gave us breakthrough designation, they said, "Okay, if you can show overall response rate in primary and secondary refractory patients of more than 30%, you have an approvable product for accelerated approval. Then we will ask you for some 2-year progression-free survival data, and we will give you the threshold that you have to meet when we see the data from your BLA filing." So we are looking forward to see that. But I think the data that I put in here already shows you that we are way beyond what anybody can expect to see in terms of progression-free survival for these patients. It's really meaningful remissions that we are seeing with this antibody. We have a pretty extensive clinical program for naxitamab. We have 2 studies, the white ones, that will start this year, and we have 5 studies ongoing. The 2 studies that we are using for the accelerated approval pathway for naxitamab in primary and secondary refractory patients. And then we have a frontline study ongoing at MSK, a single-center study, and then we are starting a multi-center frontline study also in Europe and in the U.S. And we are also having, in addition to those 2 frontline studies, an investigator-sponsored study, a single-center study ongoing in Barcelona in Spain. I have data from that study that was presented at our R&D day in December that I will share with you also today. We have a Phase II study also in chemo immunotherapy. As I just mentioned, if the patients do not come into remission on the naked antibody alone, we combine it with chemotherapy, and we can achieve quite significant responses also. And we are running a study in -- with a chemo combination to support the European registration also, the 203 study that will start later this year. And then we have the Phase II study in osteosarcoma patients also. Now if we go into frontline, which will be the next indication we would like to get into, there is a standard recommendation for treatment of these patients that when you're diagnosed with neuroblastoma, you get chemotherapy and you collect stem cells. And then you get surgical resection of your primary tumor after the induction chemotherapy. And then most of the patients outside of MSK and the sites that we are working with will get additional high-dose chemotherapy. We also give that. But then they, in addition to that, give a bone marrow transplantation. We do -- never give bone marrow transplantations. We do not consider that necessary when we follow up with the treatment of radiation and then our naxitamab antibody. So in addition, when you give dinutuximab, the other GD2 antibody that is approved in frontline, it's an 8- to 20-hour infusion. It's given in combination with IL-2, and it causes 26% of the patients, according to the black box warning from the FDA, to have life-threatening side effects. It's causing the patients, while receiving 5 cycles of therapy, to spend between 30 and 40 days in the hospitals. Our treatment is a 30-minute infusion, no IL-2, and it's an outpatient treatment. It's a completely different antibody we are using. It's a humanized antibody that has a tenfold higher binding affinity, substantially better ADCC activity, substantially better CDC and substantially better direct antitumor-killing properties. The data that caused dinutuximab to be approved was data published in the New England Journal of Medicine in 2010. And these data showed clearly that there was an effect of adding dinutuximab or GD2 antibody when patients have come into remission. We presented in December the first frontline data that we have generated. That was Dr. Mora's data in his investigator-sponsored study in Barcelona, 72% progression-free survival at 2 years and 86% overall survival, which definitely compares nicely to the data that you can achieve with dinutuximab. The difference here is that even if we consider this identical to the data set that you can achieve with dinutuximab, these patients did not receive bone marrow transplantation. And we treated these patients in an outpatient setting, and we did not give the patients IL-2, just GM-CSF. So multiple potential advantages over other GD2 targeting therapies: modest toxicity, short infusion time, ability to be administered in an outpatient setting. So we think that's a high likelihood as we continue to develop this after we get the first indication that this will also migrate into frontline use. Studies 12-230 and 201 are the 2 studies that will form the basis for our rolling BLA and for the accelerated approval. And we have, as I mentioned, orphan drug designation, breakthrough designation and rare pediatric disease designation, which means that if the product gets approved or when it gets approved, we will get a priority registration voucher that we can go out and sell since we already have accelerated approval for the type of products that we are developing. And we expect to be ready to commercialize this product as soon as we get approved. If we get a PDUFA date in October, most likely for these kind of programs, the FDA have been known to approve products 1 to 2 months earlier. So we will be ready to launch as soon as we get the approval even if it should come in August. We also developed a GD2-GD3 Vaccine in collaboration with Memorial Sloan Kettering. They had already started doing that when we took over the rights to these programs. And the background was that Dr. Cheung, who was heading the pediatric oncology, realized that some of the patients actually developed their own endogenous GD2-GD3 antibodies. So after treating the patients with their neuroblastoma and when he followed up, took samples, he could find antibodies in serum, no longer the ones that they were given for treatment, but the patients produced their own fully human antibodies against GD2. And he saw that those patients -- there were 10% to 15% of the patients, they had a much better probability for staying in complete remission for longer time. So he thought, "Maybe if I vaccinate the patients that do not develop their own antibodies, I can prevent them from relapsing." So he did that. And today, he has treated more than 200 patients. And it's a pretty simple treatment. So they give the vaccine week 1, week 2, week 3, week 8, week 20, week 32 and week 52. And what you can see here is that after the vaccination of the patients, we get up to about 80% of the patients being seropositive with immunoglobulins IgGs against GD2 and GD3. And we have a follow-up now that's almost out to 5 years. And typically, what you see for these patients that come and relapse from neuroblastoma is that progression-free survival and overall survival 4 years out is typically less than 15% to 20%. Here, we have a group of patients that has been vaccinated and followed. And we have an overall survival, which is in the ballpark of about 80% and progression-free survival of about 50%. It's unprecedented. We are planning to start a multi-center study with the vaccine also and potentially also a randomized study in frontline. This could be our third product coming to the market in the next couple of years from now. We also have this bispecific antibody, which is against GD2 and GD3, and we also have a bispecific, as I mentioned, the second bispecific antibody we have disclosed, which is CD33 and CD3. These bispecific antibodies are very distinctly different from what everybody else does when they create bispecific antibodies. You can see the construct here. I've been working with monoclonal antibodies since 1984 when I was a medical student at Copenhagen University. I did my first monoclonal antibody. I was the co-founder of Genmab. I have been in the field of bispecifics all along and followed the literature. I've been so disappointed about the results that came out of all the efforts we have done to create bispecific antibodies that could engage T-cells and bind them to the tumors and eradicate them. One of the big problems, especially addressing solid tumors with bispecific antibodies, is that we give a bispecific antibody intravenously. And we hope and expect that it will not activate the T-cells in circulation with the CD3 binding it has and let the antibody leave circulation, find the solid tumor, bind to that and then activate the T-cells there. And if you create a bispecific with one arm that binds CD3 and one that binds tumor target and you stick it in the circulation, it's a very high likelihood that it's going to bind to a T-cell and activate it before it ever gets to the solid tumor. So we are standing here today without anything that works for solid tumors in the bispecific setting. We're getting there in terms of circulating tumors, and line of sight is out there. And there's some promising data on the new CD20 bispecifics. But we created this construct together with Dr. Cheung, where we have a very high affinity, do bi-valent binding to the original tumor site, inactivation of the Fc. And then we put a little single-chain Fv with a low affinity for CD3 and hoping then when we stick this into circulation, it's going to keep the T-cell at bay. And I mean, as I said, we started in February last year. We are standing here today. We don't have a clinical hold. So we have not had any grade 4 and 5s, so it's looking as we can dose-escalate. We have dose-escalated 6 times, and we are looking very much forward to hopefully present data at ANR in May about this bispecific dose escalation study and hopefully, looking at how many times we could retreat patients because we're allowing that in the protocol and hopefully, also seeing some, hopefully, potential indication of efficacy. If that goes well, we are planning to start 3 Phase II studies with our bispecific this year. We are rolling the dose escalation study into 2 studies: 1 in osteosarcoma and 1 in third-line neuroblastoma. And then we are planning to start a multi-center study in fourth quarter this year in small cell lung cancer with a bispecific. Very, very exciting. Omburtamab, as I said, is going in for registration also by the end of first quarter. It's a B7-H3 antibody. We have 4 ongoing clinical studies. We are in the 2 studies for the accelerated pathway, the multi-center Study 101, which will support the registration for omburtamab in CNS/leptomeningeal metastasis and also the 03-133 study from MSK. Then we also have a DIPG multi-center study we are planning to start later this year. We have a DIPG single-center study ongoing at MSK. I just said that we presented data from 39 patients at ASCO in 2019. And we also have a desmoplastic small cell cancer study ongoing. It's a Phase II study we just started after we had a Phase I study with 57 patients. And this study, the DSRCT study, will also have an arm, including ovarian cancer patients relapsing in the peritoneum. So lots of exciting stuff that is also ongoing. We also have orphan drug designation for this construct. And as I mentioned, we are planning to file a breakthrough designation and planning to file by the end of March this year. What we do here is that to get the antibody into the central nervous system, there's no way you could stick it into the intravenous compartment and expect it to cross the blood-brain barrier. And in the CNS compartment, the only structure that will express B7-H3, that's the tumor cells. No normal structures express B7-H3 in the brain. So what we're doing is we're using an Ommaya reservoir and catheter going into the central ventricles where your cerebrospinal fluid is produced. And we use it as a port-a-cath, and we stick a 2 cc radioactive antibody solution as a push injection, as you can see on the central picture, into the brain of the kid or the adults that we have also treated more than 25 of. And then 2 hours later, you can see how nicely the antibody has distributed throughout the entire CNS compartment and binds to whatever it finds that's B7-H3-expressing. And for these kids, the survival possibility is nothing. 5-year survival for CNS/leptomeningeal metastasis from a neuroblastoma is 0. 3-year survival is 10%, and median survival is 6 months. So we have 3 sets of historical data we have also shared with the FDA, showing that the approximate 6 months median overall survival is what you can expect. We have an ongoing study at MSK, 03-133, where we have 107 patients. It's the biggest study in the world history. And you can imagine with 80 to 100 patients diagnosed per year in the U.S., 107 patients in the study is a lot. They had already started this study before we licensed this in. So some of the patients has been followed for 15 years. We have a 51-month median overall survival with more than half of the patients being alive. We are curing half of these kids. They are alive today. So this is really a game changer for these kids. Tiny, tiny indication but we believe it works for this. And if it works for this, it's also going to work for other B7-H3 positive CNS cancers, including the DIPG patients if we get up to the right dose. So this is very exciting, and as I said, it goes into registration, and it will be supported. We'll get a post-marketing commitment to come back to the FDA and show in our multi-center study that we will have at least significantly better than 10% 3-year overall survival. We already know that we will get that. So we also realized that there's a number of other patients, including adults that have CNS/leptomeningeal metastasis. We're getting so great at treating systemic cancers that we eradicate the systemic cancers. And tumor stem cell sneaks into the central nervous system, and then they start growing and then end up killing you. You have no chance of surviving that. There's basically nothing that will cure a CNS metastasis from most of the systemic cancers. You can find some rare exceptions from maybe a kidney cancer or so that gives solitary metastasis. But the rest of the 99% will die. So if we want to address thousands and thousands of patients with CNS cancers, we cannot use an iodinated product. It takes 2 to 3 hours to do the iodination and the quality control and then we can ship it. So we decided to say, hey, why don't we use a much simpler way of radiation. Why don't we use lutetium-177? We put a chelator on the antibody. We used the same antibody but with the chelator DTPA. It takes 5 seconds to radiolabel because the DTPA will chelate the lutetium-177 and it's radiolabeled. So we decided to do that, and we filed the IND for this construct in December. And in second quarter this year, we start a medulloblastoma to stay true to our pediatric commitment study, where we have already treated in the iodinated portion of the antibody, 27 patients for medulloblastoma, seeing some quite interesting positive results. So now we go for that as a potential fast track to the market for the new omburtamab construct with lutetium labeling. And as I said, then we start also in third quarter this year an adult study, a basket trial for B7-H3 positive adult patients with CNS disease. So we also have a commitment to actually be able to sell these products. So we have started about 20 months ago to build a commercial organization, and we will be ready to launch the products as soon as we get approval from the FDA. We are building the best-in-class rightsized commercial organization, we believe, and we have launched planning and getting ready for execution. And we should -- we'll be focused on a rapid uptake of our antibody, optimizing price and reimbursement, and we're working with all these things with the stakeholder experience also. And we are, of course, also building awareness about Y-mAbs to both hospitals, both key opinion leaders and also patient groups, et cetera. And we are showing increased presence at conferences and scientific meetings where these diseases are discussed, most recently at SIOP but also of course at ANR and at SIOP later this year. Financially, we have been fortunate enough to have very strong support from our investors since we started the company. We have, since we started the company in August 2015, raised a total of USD 374 million. We did an IPO in September '18 and raised $110 million. And then we did a follow-on offering in the end of October, closing at November 1, '19 and raised another $144 million. So pro forma on October 1, which is the latest financials we had, we had $233 million in the bank. And as I said, that should be sufficient to bring us into a situation where we get at least until 2022, where we hopefully will have some reasonable commercial sales from our products. As I mentioned, we have PREs that we will receive for both our lead assets. The going rate right now for a priority registration launch is about $100 million. We are sharing the first one we get with MSK from where we got these licenses, 60% to us, 40% to MSK. The second PRE would be shared with MSK also, 67% to Y-mAbs and 33% to MSK. So potentially, those 2 PREs can give us more than $100 million in additional nondilutive cash contribution. So financially, I think we are in a very fortunate situation. And finally, as I said, I think for us, the 2 key events this year, of course, is the BLA filings of our 2 lead assets and of course, also to see the data from our first bispecific antibody when we present, hopefully, the data in May at the ANR meeting. Unfortunately, I'm not at the Abstract Committee, so I cannot guarantee the abstract will be accepted, but I certainly hope so. Thank you very much for listening and for your interest here.