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

Welcome, everyone, to the 41st Annual JPMorgan Healthcare Conference. My name is Tessa Romero. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Taylor Hanley and Adhiraj Chauhan from the team. Our next presenting company is Y-mAbs Therapeutics. And speaking on behalf of the company, we have Founder, Thomas Gad. Before I turn it over to Thomas, I just wanted to highlight for that -- for the Q&A after this formal presentation, there is an ask-a-question button in the portal, and I'm happy to ask the question on your behalf. We will also be taking live questions here in the room. So with that, Thomas, over to you.

Hello, everyone, and thank you for listening into today's presentation of Y-mAbs Therapeutics. Y-mAbs is a commercial-stage biopharmaceutical company founded on technology spun out of Memorial Sloan Kettering back in 2015. Today, we have 1 commercial asset and a couple of platforms that we are developing, and I'll go through that today. But before we start, I want to make your attention to this disclaimer for forward-looking statements. So yes, our mission has been from the start to develop better and safer antibody-based oncology products, and we address clear unmet medical needs in pediatrics and our strategy is to out-license adult indications to [ refind ] pediatric indications. I just want to give a quick update on our recent CRL letter we received in late November of 2022 on our second lead, which was omburtamab indicated for CNS metastases for high-risk neuroblastoma, which is a ultra-rare indication, approximately 6% to 10% of high-risk patients relapse. Unfortunately, we got a CRL, and we are having a Type A meeting actually tomorrow. We also file that in Europe, and negative opinion was issued referring to randomization of that drug. So based on that CRL, we've made some recent changes as we press released last week. We have redefined our focus. We continue to focus on DANYELZA, which is approved in the U.S. for relapsed and refractory high-risk neuroblastoma in second line. And we are also focusing on additional label expansions and indications into osteosarcoma. And lastly, we are looking at other adult indications, but only through ISS in order to create proof-of-concept and then seeking partnerships with these indications. We continue to expand the commercial footprint of DANYELZA throughout the world, ex U.S. sales growth through partnerships. One of the most important milestones that happened last year. We got approved in China with SciClone Pharmaceuticals, and we are very excited to launch DANYELZA in China, late first half this year and going into second half. We have also filed a BLA in Brazil. We filed that in September 2022. So depending on rounds of questions and responses that could come online third quarter, fourth quarter this year. Besides that, we have licensed in a completely novel and highly differentiated radiopharmaceutical platform that was developed by, again, Memorial Sloan Kettering and MIT, and we are going to come back to that platform as well later on this presentation. So what we've done is we've planned to be very conservative with our cash. We have deprioritized some programs and really focused our cash and extended our cash run rate into 2026 by completing a reorganization that included 35% layoffs and up to 30% cost-cutting program. So focusing first on the DANYELZA. We have started to see some very, very positive trends in Q3 that continued in Q4. Just to name a few of these. The neuroblastoma market is highly concentrated in the U.S. Approximately 60 hospitals represent 75% of the GD2 market centers of excellence. And what we are seeing now is that 2 out of 3 new patients currently are coming out of these high-potential category hospitals. 27% of these hospitals have also dosed at least 1 patient, so you can see there's a potential of good growth in that area in order to get up to the 60-plus sites. And at this point, 50-plus hospitals have actually dosed with DANYELZA in the U.S., and a very important status also that nearly 20% of hospitals have now dosed more than 2 patients, which is very important. And also, the percentage of patients that have received 5 cycles is growing nicely, and the percentage of patients who've received 8-plus cycles is also starting to grow. So very positive trends. Initially, we expanded the market in the U.S., and that tells you we will probably use mostly in third line. But now we've taken 12% of the market. And that shows us that we are getting more close to being used in second line [ income ] also in some third line, but in second line, that leads to the average cycles of increasing, which is what we want to see so you don't have an efficacy dilution by being used in third line. And coming back to the milestone of SciClone, they have a dedicated 15-person team, targeting 40-plus hospitals and a very strong KOL engagement plan. In China, [ Cartiva ] was approved, I believe, last year. But other than that, the GD2 market, we believe, is very highly important and significant over there. What are we doing with the front line? So neuroblastoma, initially on the -- when you're diagnosed, you are -- as a high-risk patient, you will see 5 cycles of induction chemotherapy in order to shrink the tumor. You then get surgery, additional chemotherapy. And if you're in full remission, you get moved to maintenance GD2, which is where Unituxin is approved. And what we have done together with our KOLs, is an ISS study, we have actually moved DANYELZA up in the induction phase in order to see improved responses prior to surgery. So that's scientifically very important. And it also makes a lot of sense as the clinicians start to use your drug early on in combination with chemo. And obviously, if you're successful, you will use it on the back end, too. So it's a very exciting study. It's 40 to 50 sites across North America. It's 76 patients. We started enrolling back in September. And the first interim look is September 2026, and that's the first possibility to go for label expansion if that works out. Other than that, MSK has fully recruited a single-center frontline study, which we hope will read out, and probably our newest, very soon. So DANYELZA, we have a strong focus on at this point in time. We have the ongoing confirmatory study as we received an accelerated approval on tumor responses, 201. Then we have the ISS study. I just told you about, moving it up in front line, and then the next indication that we are looking at is very exciting. It's relapsed second recurrent osteosarcoma, pulmonary only. So when these patients relapse, the second time, they relapse in the lung, they get surgery, but they relapse again very frequently. And then there's nothing -- there has been no new treatments for decades in this disease. Front line treatment is 5 chemo agent regimen. And if that's not successful, it's a bleak outlook for these patients. There is no other anti -- GD2 antibody in this setting that we are competing with. So that makes it even more exciting. At this point, we're not doing any development for large indications. What we are doing is we are giving drug to ISS, reverse inquiries, and we have some of those. And if they show proof of concept, then we would like to partner out large indications, but we are not, as a company, doing anything ourselves on that. So DANYELZA, just for pediatrics in the U.S. alone is a peak revenue, annual revenue drug of more than $400 million, and we are very focused on getting to that point, and that would include osteosarcoma and then you can discuss. So this drug will eventually potentially make the company breakeven depending on how much R&D we gear up with SADA or what partnerships we make. But we have full focus on growing the top line of DANYELZA at this point in time. So coming to SADA, it's a radiopharmaceutical 2-step platform. It's highly differentiated. It's novel. There is nobody out there doing what this platform is doing, and there was lots of attention on radiopharmaceuticals finally. So that's good news. We see some strong results from some of the other players out there, especially Novartis and Pluvicto, was great. And so we would like to go through this platform and show you why it's very different. This was developed by MSK and MIT in conjunction, and we licensed it in 2020 in April, and we have invested a large amount in the CMC part of this platform. We optimize the platform, and we have -- it's fairly derisked in terms of the manufacturing at this point in time. So the platform works -- I mean, in layman's terms, it's a 2-step platform. So initially, we have a tetramer -- I'm going to skip that. That looks like this. It's a protein-only infusion. Once it goes into the bloodstream, it attaches strong binding to the tumor. And whatever doesn't attach clears rapidly out of the bloodstream. So then we wait in the animal models, 24 to 48 hours, and we extend -- administer an isotope. We use lutetium in this case. The platform is highly modular, so you can change the isotope and you can change the antigen, obviously. So you can -- it's not completely too [ magnostic ] because internalizing targets are not great. But other than that, it's very, very modular. So when we administer the isotope, it can only bind to the protein that is attached to the tumor. And we get some very, very interesting therapeutic indices with no tox, very elegant, no kidney, no bone marrow and no liver tox. So this is really very exciting. I'm not going to spend -- this is some preclinical. It just shows that highly aggressive cell lines Memorial has worked on, and it just shows that these tumors are pretty much melting away. It's very impressive, but it's in animals. So we're not in humans yet. We have opened up the first trial, and it's an interesting trial because it's a theranostic trial, so we can derisk this program early on. So here, you see the difference of traditional 2-step versus a SADA, 2-step, as you have no circulating protein in the bloodstream with SADA. So you get a very precise uptake on the protein that sits on the tumor, and that's the whole elegant mechanism of action with the 2-step process. The portfolio that we got approved and are now running a Phase I for small cell lung cancer, melanoma and sarcoma. It's a 3-part protocol. Part A is the dose escalation of the protein. Part B is the dose escalation of the isotope in between Part A and Part B is an imaging dose of 30 millicurie. And that means that a patient that doesn't light up on the SPECT scan does not get to move to Part B. So we hope we only treat patients that will benefit from this. The dose escalation actually starts at -- it really starts at 200 and then it goes up to 400, all the way up to 750 , and I think it's very impressive to see a protocol that was allowed to start at 200 millicurie where many other companies end because of limitations. Part C is repeat dosing and up to 6 cycles, but it's really up to the physician at that point in time. If we get that far, they can use this, and we can -- we have shown in animal models. We're going to repeat those without having to wait because of tox. So very interesting. So what we are doing with this platform is we are, as I said, getting into humans now. We are hoping to derisk the platform early on. And then our strategy is to out-license large indications, such as small cell lung cancer, melanoma. And our second asset is CD38, and we hope to file the IND this first half of 2023. And commercially, this platform has a huge advantage as well as you can use large infusion centers because of the protein infusion, and then the oncologists can send their patient to the local academia for the isotope infusion, so we don't have to go directly to nuclear medicine. And another advantage is that we don't have a patient-centric dose. So if a patient doesn't show up, we can actually use another patient. We don't forego that dose, which gets very expensive. I could speak a lot about this platform, but we're running out of time. So very exciting. We have many more targets, and we are working on partnerships. And we believe that when we validate this in humans later this year, we would be able to also look at third-party targets, failed Phase III targets and other avenues with this platform. Financial summary. So we guided that we're going to end up $47 million to $48 million for DANYELZA this year, which is great. We guided $60 million to $65 million next year, which I dare to say, is conservative since fourth quarter was $15 million. And then we've cut cost up to 28% and reduced our cash burn and made sure that we have able cash to execute these milestones coming this year and next year, and we ended this year with $106 million in cash. So I will skip all this and show you what we believe Y-mAbs is and how this is going to develop as a company where the current situation is ex U.S. partner sales, franchise by adults and then SADA will eventually outgrow the value proposition. And with that, I think I used my 20 minutes. Thank you.

Great. Thank you, Thomas. I'd like to welcome Bo Kruse, CFO, up onto the stage. Bo? I'd just like to remind folks, just to wave your hand on me if you have a question. But I'm just going to kick us off here. I thought maybe we'd start the discussion here on commercial. So where has the DANYELZA launch in relapsed/refractory high-risk neuroblastoma sort of exceeded your expectations? And where has it might be falling a little bit short?

Yes. So I think we launched a product -- we got approved in November 2020, and we launched it in February 2021. It was a complete virtual launch, and initially, we went through after only the highest growing sites in the U.S. And I think doing that, we realized that there was a drug that was approved in 2015 called Unituxin that had been on the market for 6 years. And since we launched in COVID, there was a shortage of nursing staff, and you don't switch from inpatient to outpatients. You run both programs when you start. And so I think initially the limitation of additional staff and being virtual was very difficult for the product. Then we relaunched it when we hired our new Chief Commercial Officer in 2022, and she's done a phenomenal job. And where we've exceeded is -- I really see some very positive trends that, cross our fingers, is going to continue in Q3 and Q4.

Great. And Thomas, maybe you could talk a little bit about how has the commercial strategy changed with Sue, and kind of what are the key initiatives that she's implementing for the launch?

Yes. So initially, it was a purely virtual launch, and it was going after Slide 1 and down to Slide 10. After logging on these doors for a while, we changed that and we went after smaller volume Unituxin sites as well as we are an outpatient treatment, and we set up a very nice nurse education program and so forth. And we also added -- so we buy scripts. So we can come in early and see when a doctor diagnoses a patient. So in rare disease, it's very important you follow the patient and kind of fill the form and put that patient into the system in order to potentially get a treatment eventually. And that's what Sue has implemented. And we are continuing to implement new strategies for '23 as well, including bone and bone marrow disease. So that's another new area of growth that we can attack.

And maybe you could give us an update a little bit on the dynamic between Unituxin and DANYELZA because we know that's relevant for the launch here. So what's the latest market intel on that point?

Yes. So I think Unituxin is predominantly used in front line and in refractory patients at this point in time. So we are going after the refractory patients. So the patient journey is the 5 cycles of chemotherapy to shrink the tumor, its surgery, then there's additional chemotherapy and then maintenance. And the people who do not -- patients who do not respond to initial induction chemotherapy, those are the ones that are also included in our label defined as primary refractory, and we have learned that bone and bone marrow disease are the 2 most persistent so we can go out for these patients. But right now, I would say, Unituxin owns front line and refractory, and we are predominantly getting into second line where our label is and less of a third-line option.

Okay. And what are the key geographies that are expected to come online in 2023? It sounds like China is a key one, but are there any other ones that we should be thinking about?

Well, we have numerous other smaller countries. But I think notably, of course, China is the main event, ex U.S. And then I believe Brazil, I mean, we have a great partnership covering Lat Am with Adium, also called Techno Pharma. And I think that opportunity in itself is also quite a nice opportunity. As I said before, we filed Brazil and we filed a few other, but Brazil is the notable country. And hopefully, that will come online late this year.

Okay. I'm curious, maybe we could chat a little bit here about the opportunity in newly diagnosed high-risk neuroblastoma. What's the latest thinking on kind of your clinical development strategy there? And what do you think might be required to secure an approval in newly diagnosed patients?

Yes. So the strategy we've taken is that Memorial has the fully recruited frontline study. We are waiting for that to read out. Once that reads out, there will be scientific literature and hope their compendia listing. As pediatric in the cases in the U.S., they can get reimbursed across label if you file paperwork, if there's literature to refer to payers, payers will reimburse. So what we have done there is, I'm going back to that ISS study, we're trying to move DANYELZA way up in front line. So even before Unituxin's frontline because we are moving it up into the induction phase. And if that's successful, and it shows better long-term survival because of the tumor responses prior to surgery, you would clearly think, hope and believe that DANYELZA would be used in induction and also on the back end as a maintenance therapy. So that would -- it's 5 to 7 cycles on the label, and open induction, it's 5 cycles of chemotherapy together with DANYELZA. So that's 10 to 12 cycles.

And maybe it makes sense just to touch on guidance a little bit here. You gave guidance -- I can't remember what week, I think it was last week, but it's been a long couple of days. So what are the key assumptions underlying the $60 million to $65 million in net rev guidance for the year -- for 2023, which I think that implies about a 25% to 38% projected growth rate over what you should do this year?

Yes. So what we assume is we assume that we are going to move further into second line and get the average number of cycles up and grow the market that way. And then we are also assuming that we're getting into the -- it's really a failed induction patient, the ones we call refractory patient. So those are the assumption. But we are quite conservative, but I think that's good. The fourth quarter was $15 million, and we guided $60 to $65 million. So hopefully, we can see some more like Q1, Q2 and come back up and reaffirm.

And Thomas, can you just remind us what is the average number of cycles that you're seeing right now in the clinic?

Sure. So the issue with that is that I think 50-plus percent of our sales are coming through Memorial Sloan Kettering, and they do not use our hub. So we don't get a lot of intel on that. However, I know from the clinical trials that the average cycles were 5 plus. And I know we're not there yet. I think we have -- we've grown 20% compared to Q1 and Q2, but I think we're still at maybe 3.5 or 4. I'm not exactly sure where we are, but there's plenty of room and also for the patients who receive. When we did market research, we saw the Unituxin was used 6 to 11 cycles. So let's say for argument sake that we used a 3 to 5 -- 3 to 3.5 cycles on average. We have lots of the work to be done there.

Okay. Okay. And I think you've talked a lot in the past about sort of these other indications where DANYELZA could fit in. And I think you've talked also about partnering those indications. They're finding the right partner. So how is progress towards finding a partner for other indications? And is that a near-term priority for Y-mAbs?

Yes. So osteosarcoma is not a partnership opportunity. It's a global study with 140 patients spread out between U.S., Europe and China. And there, we have SciClone as a partner in China. In the U.S., we are not looking to partner that up. And on the large indications, we are not being proactive there. We are doing it through ISS. So if we create proof of concept, we will not do anything ourselves. We will want to have a company because you would also need to change the dosing schedule for adult indications to like day 1, day 8, day 1, day 16. So we want to see proof of concept. And when we have that, we can find the appropriate partner to position the drug. But the priority is label and indication expansion for DANYELZA and then derisking SADA and find partnership for SADA.

Okay. And maybe we can switch gears here and talk a little bit about omburtamab. Just touching on it briefly. It sounds like the base case here for you guys is that the program could be deprioritized. But is there a scenario where it could be not deprioritized? Or can you just kind of unpack how you're thinking about this program strategically at this point?

Yes. So I think it's pretty evident what the regulators both in Europe and the U.S. are looking at, and that is randomization. We know it's a high unmet medical need, ultra-rare indication and patients who do not get this drug probably looking at not long-term survival. So randomizing is very difficult. So what we are doing is we are saying we're deprioritizing it, we are finding a partner for it or we're getting another -- a financial partner or a thing in that nature unless we have this Type A meeting with the FDA and we get to another conclusion where we think we have a clear path. But I -- we've said it in the press release, it's been -- it's already been deprioritized for the future unless something would happen, unexpectedly.

Okay. And maybe we could -- well, any questions from the audience?

I wanted to ask a question on the SADA platform. I was wondering how many sites are you enrolling at currently. And have you dosed your first patient?

We have 2 open sites. We're opening 6 sites, and we are screening for patients, and we have not dosed the first patient yet, but it's imminent. And the plan is to expand beyond 6 sites in the second half of this year.

Thomas, in your presentation, you showed a little bit about the preclinical characterization of the SADA constructs, ultimately, what makes you the most confident that this platform is differentiated?

So the therapeutic indexes and the thresholds to normal organs, the acceptance level of rate activity that you -- the normal organs can -- we are not near any of those limits in the animal models. And the whole issue with rate of pharmaceuticals is that you have continuous IgGs or whatever [ construct gap ] floating around the bloodstream. So it keeps passing the bone marrow, and it creates myelosuppression and other things. And we don't see that because it's a 2-step. So we get very -- the whole plan is that it's, there's no protein left in the bloodstream, unless it sits in the tumor. So that's what's so interesting. And then I think the possibility to derisk it early on is very attractive as well because of the imaging part of the study. So we can probably derisk these programs, I mean, way earlier than therapeutic programs at least, so...

And can you just frame a little bit for us how many patients do you think you might show an initial data set? And kind of it sounds like potentially that could happen sometime this year, but just sort of frame for us what initial data might look like.

Yes. So obviously, this is collecting of scans. So what we need to do with the protocol is designed from the FDA. So Part A versus Part B, there's 5 days in between for the first 3 patients, then it narrows to 3 days for the next 3 patients. And then we should be in the optimal window of 24 to 48 hours. And if we can show -- as I showed with the spinning mice, I call them, if we can show equivalent precise tumor uptake, strong tumor binding and the imaging dose lighting up that protein on the tumor and clean nowhere else, that's a validation of the mechanism of action. So that's what we're looking for.

And that could happen this year, you think?

Yes. I mean, I don't know, it depends on how quick the patients come in. But absolutely, yes.

Do you have a base case for how quickly you think you can enroll?

Well, we definitely want to be there by R&D this year, but maybe even by summer if we are lucky enough to get the enrollment going.

Okay. Okay. Any questions from the room? And it sounds like you've talked in the past about maybe securing partnerships for some of your SADA constructs. I mean is that kind of a key near-time priority for the company?

Yes, I think a third-party validation of that platform is very important for the company. We are too close to in human data, so we probably have to wait until we have that before doing that.

Okay. And Thomas, I think you took the interim CEO seat at Y-mAbs. So just kind of curious, could you give us an update about how it's going towards finding a new CEO? And what are you looking for specifically to kind of lead Y-mAbs in kind of the next stage of the company?

Yes. So I think things have changed a little bit since we got the CRL letter. So we did a reorg. We want to get through that. We want to position the company. And then I think in the second half of this year, we would most likely look for -- I think the profile has changed a little bit due to the event. So we would look for something more radiopharmaceutical R&D type of experience. But at this point in time, we are just making sure that they're going through the recovery from the CRL and moving forward on our most important programs and then get ready for somebody when that's been cleaned up.

Okay. And how should we think about the 28% reduction in operating expenses and 35% reduction in workforce? Will these reductions happen all at once or will they be more spread out throughout 2023?

So the restructuring as such will basically be taken care of during the course of the first quarter. So that would be nearly all of the cash flows impacting the first quarter and all of the P&L impact is in the first quarter.

And another question for you, Bo. With $160 million in cash as of the end of the year, you've noted cash runway into the first quarter of 2026. So can you just walk us through what is assumed with respect to revenue contributions and any projected milestones for the company in that time period?

Yes. So we generally try to be very conservative in coming up with these forecasts. So in terms of revenue growth, we basically assumed an only 10% increase year-over-year-over-year, so that's very conservative, especially considering that during '22 from the second to the third to the fourth quarter, basically we saw 20% per quarter, but we try to be very conservative for that. And of course, the expenses are also important in this context, and we would expect the expenses to remain very constant for the next couple of years.

And are there any milestones from any of your partners that we should be modeling or thinking about?

That would be immaterial for this purpose.

So before your most recent restructuring, I think at your R&D Day, you extended your cash into 2025. So that was maybe an extra 6 months of cash. And you noted that, that was due to conservative financial planning, can you provide more detail on what that included? Or was that just part of what was reflected in the more recent restructuring?

Yes. I think when we said '25 at the R&D Day, we were basically in the process and we continue to refine cost or more cost cutting, laid off additional employees. And in its final form, it's basically just 3 years of cash from now. So I think we ended up in the right shape with a very lean company going forward.

Any other questions from the room?

Sorry, I just thought of another one. For the -- I believe it was the MSK study. And I think at R&D Day, you were saying, or guiding that there was going to be a publication soon. Is that still coming out soon?

Yes. It's coming out soon but -- so we don't control that. Investigators at MSK control that. The only thing we know is that it's fully recruited, and it's an abstract that's being filed soon. So we hope at a suitable venue that they choose, it will come up, but yes, it will be soon. I don't know when but it will be soon.

All right. Well, thank you, Thomas and Bo for the discussion here and for joining us today. And I want to thank all of our audience members as well for listening, and I hope everyone has a great rest of the conference.

Thanks for having us.