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Hello, and welcome to Nuvation Bio's Fourth Quarter and Full Year 2020 Financial Results and Corporate Update Call. Today's call is being recorded, and a replay will be available. [Operator Instructions] Now I'd like to turn the call over to JR DeVita, Executive Director of Corporate Development and Investor Relations at Nuvation Bio. Please go ahead.

Thank you, and good afternoon, everyone. Welcome to the Nuvation Bio Fourth Quarter and Full Year 2025 Earnings Conference Call. Earlier today, we released financial results for the quarter and year ending December 31, 2025, and provided a business update. The press release is available on the Investors section of our website at nuvationbio.com and a recording of this conference call will also be available on our website following its completion. I'd like to remind you that today's call includes forward-looking statements, including statements about the therapeutic and commercial potential of IBTRO

Thanks, JR. Good afternoon, everyone. Thank you for joining us. 2025 was a pivotal year for Nuvation Bio, and I'm pleased to discuss our full year and fourth quarter results with you today. Our most significant achievement occurred on June 11 with the full U.S. FDA approval of our first therapy IBTRO

Thank you, David, and good afternoon, everyone. I'm excited to report that the launches of IBTRO

Thanks, Colleen, and good afternoon, everyone. For detailed fourth quarter 2025 financials, please refer to our earnings press release, which is available on our website. Now let's go over some important highlights of the quarter. I'm pleased to inform you that in the fourth quarter, we generated $41.9 million in total revenue, including receipt of the milestone payments, which brings our total revenue for 2025 to $62.9 million. These figures include $15.7 million and $24.7 million in IBTRO

Thanks, Philippe. When I take a step back and reflect on our 2025, what gives me particular confidence is the foundation we've built for what comes next, an increasingly durable commercial franchise, a pipeline with meaningful long-term potential and a capital position that allows us to execute with discipline and flexibility. I'm incredibly proud of the team and grateful for the support of our investigators, partners, shareholders and most importantly, patients as we continue this journey into 2026. With that, I'll ask the operator to open the line for questions.

[Operator Instructions] The first question comes from the line of Farzin Haque with Jefferies.

Congrats on the progress. So you're not providing any revenue guidance yet for 2026. But what are you seeing in 1Q in terms of first-line and second-line plus mix that gives you confidence in meeting the consensus mark of $150 million for the year?

Farzin, thanks for the question. This is David. So we're -- as we said, we feel that the patients are out there. We think that the robustness of the first 2 quarters shows that we are able to capture a lot of -- a significant number of these patients. Just -- if you look at the number of new patient starts, we think the trajectory has been pretty good. As we did say, the majority of our NPS, our new patient starts to date have been later lines, as you would expect. But we are seeing increases in first line news. But we've also made the point previously that we don't have visibility into the majority of these patients. because unless they come to the Nuvation Connect Portal, we don't actually necessarily know -- what we need to know about them to know what line of therapy they are. But what we've seen we do see a majority of our use currently in later lines of therapy. Clearly, those aren't the ultimate price. Those patients, especially in the third-line study, have relatively short durations of response. And so that would lead to a much higher discontinuation rate. In fact, the vast majority of the discontinuations that we have seen are due to these late-line patients. But we are confident that over time, we're going to see growth moving toward to the second line and then to the first-line setting. And so we think that the patients are there and we think that ultimately we will start to see first-line use a much longer durability and then the revenue stack that we've previously talked about.

Perfect. And then for safusidenib, can you provide an update on the current enrollment trajectory for the Phase III? And do you anticipate any interim analysis before the projected 2029 completion?

We haven't commented on our enrollment. Those patients are definitely there. As you know, there's absolutely nothing for high-grade disease or vorasidenib approved only in a subset of low-grade disease. So we think that, that trial will enroll well. But it is a PFS study. So it's going to take a while to get the number of events we need to see it -- to see the results. So that's why we've guided to a 2029 readout for that. But I would say that the patients are there. We feel very confident in the capabilities of our clinical operations and clinical development team. So we think that trial will enroll on target. We will not be any later than 2029 in reading that result out. And also -- I'm sorry, we don't have any plans right now for interim analysis. I forgot to mention that.

The next question comes from the line of Leonid Timashev with RBC.

I just want to ask a little bit more about the IBTRO

The data set that we discussed, the seasonality was still based on just ROS1 TKI use in the last 4 years. So while there was a somewhat lower use in the fourth quarter, I would say, it's hard to know if that would necessarily predict about what's going to happen going forward. We feel confident the patients are there. We know -- we know that from -- just from our interactions with all the centers that we're at, these patients are there. We think that with -- while there's always way to improve the amount of genetic testing, we think that new patient diagnosis will happen. We know there's a prevalence pool of over 1,000 patients who are TKI experience. Clearly, those are the ones that are the -- going to be the easiest ones to identify because they've already been on our ROS1 agent. And clearly, we've already captured a significant number of those. But so I don't really know if the seasonality will necessarily result in a bounce back. It could, but I can't tell. And as you know, we just had a significant blizzard recently. So that was a pretty significant weather event. But, I don't, again, know if that will change anything.

The next question comes from the line of Michael Yee with UBS.

This is Matt on for Mike. I wanted to ask on your expectations just kind of further trajectory cadence of patient uptake for the year, especially with maybe a competitor entering the market in the second-line setting, later in the year. How do you expect to see kind of the market shake out? I know you guys talked about TRKb as an important factor for you guys? Just kind of speak to the longer-term competitive landscape here would be great.

Sure. Well, as you've already seen from the first 2 quarters that we're over 200 new patient starts per quarter so far, and we think that's going to continue. And I've already said that the majority of those are later line therapy. So if you talk about second or third line, we've already captured a significant amount of about 1,000 TKI experienced patients that we believe are out there. So -- by the end of the year, we think that we will have probably captured a significant majority of all those patients. And as I said, what we're looking for is growth in the first-line setting. And given our 50-month duration of response, which is unmatched and our tolerability profile, we would expect to claim the majority of that. So that's what we're really looking for. We're not really looking any more at later-line use because that's -- we've been there and we've actually captured much of that. But we're looking towards the first-line growth, and that's what everyone should be focusing on. I think the one of the most compelling features of our drug is its durability. As you know, patients and doctors decide on therapy based on efficacy and by far, the most important metric for efficacy is how long that drug will work. We think that TRKb is an important factor in durability. If you look at the lorlatinib data, there is no TKI with longer median PFS that lorlatinib in the CROWN study, which is over 5 years. And lorlatinib has significant TRKb activity. And if you look at CNS control rate, it's really high. And as you know, for a cancer like ROS1 lung cancer, which is so CNS tropic, where it starts in the brain more than 1/3 of the time and goes to the brain another 50% of the time. It's really important to have as robust control of the CNS as you can. And we think that TRKb will play a significant role there. And as I've discussed previously, if you look at our intracranial response rate and our second line setting at 66%, that's not been matched. There's nothing close to that. So -- we think that the profile of this drug is extremely compelling, tolerability, efficacy, we're looking to move the first line, and we think that's where the unmet need will persist after we've already taken care of the later lines of therapy, which we are capturing. So we feel bullish. We feel we're just where we need to be and things are heading in the right direction.

The next question comes from the line of [ Mary Coleman ] with Clear Street.

Congratulations on the progress. For taletrectinib or IBTRO

Sure. So we did note that if you look at the other TKIs that before we were approved, we actually did see an increase in scripts in the other TKIs after the NCCN guidelines came out. So I think those guidelines were helpful, and they did increase TKI use. Now since the introduction of IBTRO

All right. That's helpful. And for the Phase III astrocytoma trial, what efficacy outcomes would be considered both clinically meaningful and commercially attractive. And -- what is the kind of estimated market opportunity or value that it can provide? And for the other cohort, what was the rationale for adding the oligodendroglioma patients as a separate cohort? And how might this become a value-generating program?

Yes. That's a great question. So when I think about glioma, I divide it into a pie about 50-50 low grade on 1 side and about 50% high grade on the other side. But within those subsets, you can divide them again. So each side, both the lower and high grade have a low-risk and high-risk features. Currently, vorasidenib is only approved in 1 of those pieces of that pie. It's only approved in low grade, low risk. That means what remains for an opportunity is high risk, low grade, low risk; high grade and high risk high grade. So the Phase III study that we're doing targets 3 of those parts -- 3 pieces of that pie. Instead of the vorasidenib 1 piece, our Phase III trial targets 3 of those pieces. So we think that's a very significant unmet need for patients. It's clearly a much larger commercial opportunity. And so we -- to get that drug approved in those 3 pieces of that pie, we have to do an overall -- we have to do a progression-free survival study, which is why -- we just need to enroll a certain number of patients. We have to follow them for a certain amount of time, and that's why the readout is 2029. Now that said, we also think that it's important for us to get this drug out to patients as quickly as possible. And there is yet another piece of that pie that isn't currently being adequately addressed, which is -- if you look at all grade 3 oligodendroglioma patients, these patients are a little bit different because unlike the Phase III study patients, which I talked about, those patients have completed surgery and radiotherapy and somewhere between 6 and 12 cycles of temozolomide. So as a result, they don't tend to have measurable disease. When you don't have measurable disease, you have to use PFS. You can't use response rate. Well, clearly, response rates are much faster readout than PFS. So the grade 3 oligodendroglioma study is important because those patients have measurable disease. These are patients who have not had a resection or not a recent one, have, in general, significant measurable disease, and they just can't take because these patients can live 15-plus years, they just can't take chemotherapy or radiotherapy every day for the next 15 years. I mean it would just be impossible to tolerate that. So we think it's a huge unmet need. But because now these patients have measurable disease, we can use overall response rate, unlike the SIGMA Phase III study, which is a PFS readout -- this will be an ORR, an overall response rate readout by RANO 2.0 criteria. So we think that if we can see a significant response rate in that study, and we've guided to reading that study out by 2027. Clearly, that's a much earlier readout. We know there are examples of all the glioma drugs being approved on a very small data set with response rate, we know that day 1 glioma drug was approved on less than 80 patients with an overall response rate. So clearly, we see a really robust response rate. We think that would -- that would justify a discussion with FDA as to what would it take to get this drug approved to get it to patients a lot sooner than a readout in 2029 for the Phase III study. So we think that it's important to do the study because, number one, it's a really important unmet need. These patients just cannot take chemo and radiation for 15 years. That's just not tenable. They need something that's much better tolerated, much more convenient. And secondly, it gives us an opportunity to see the activity of this drug in an area where nothing else works. Vorasidenib has no responses in this highway population. The response was literally 0%. So we think that it will give us an opportunity to look at the response rate of this drug and potentially initiate a discussion with FDA to just figure out how to get this drug to patients even earlier. We also think that generating data in this subset were nothing works and even vorasidenib has a 0% response rate will compel physicians and patients, who think, hey, this is a drug that has activity where nothing else does, should -- is this a better drug. Is this a more powerful drug. Is it to do things that other drugs can't do. And we think that could potentially influence the glioma market and the practice of what position the patients decide to use or attempt for treating a disease that has relatively few treatment options that is still, at the end of the day, an invariably lethal disease. So we think that the second study is a very important study for all of those reasons.

The next question comes from the line of Mayank Mamtani with B. Riley Securities.

Congrats on the progress. I appreciate the level of detail on IBTRO

So we have said since our very -- since the first quarter that we reported sales that we would continue to look at new patient starts. I think that's an important metric. It's particularly important in the first year where depending on the mix of patients and the duration of response or the rate of discontinuation, your revenues will not necessarily track with your new patient starts, especially as an example of your a third-line patient you just continue in a month or 2, you're not going to have the kind of revenues that you would expect in the first line setting. So we think it's important, and we said this since June 11, when we got approved, that we would focus on new patient starts at least for the first year because I think that's the best metric is our patients using this drug do physicians who want to prescribe it. And over time, what you'll see is that we've said there's only about 1,000 or so TKI-experienced patients. So if you see -- if you continue to see 200 patients per quarter, and we know that at some point, we're going to have captured the majority of that 1,000 patients. That means any growth at all in that 200 number has to be in first-line patients. And while that revenue may not appear immediately because it takes you a year to get stacking. When you start to see that growth in first line, you will see over time revenue stacking. And you will also see a significant increase in revenue. It's just not going to happen immediately because those third-line patients are going to come off, some of them discontinue within a month. And we think those first-line patients will be on for 5 months. So I think that for the next few couple of quarters, we still think NPS is important. But a year into our launch, so by third quarter of this year, we'll have been doing this for a year, and we continue to get 200-plus patients per quarter, and the majority of those are TKI experienced. That means we will have captured the majority of the TKI experience market. So any growth at all in that NPS number has to, by definition, be in first line. So I think that's what you should be looking for. I think the revenues will catch up to NPS with a few more quarters. It's just not going to do it right away, but that's what you would expect.

On the discontinuation on the earlier line.

Oh, yes, sorry. So 75% of our discontinuations came from late-line patients. So -- so very late.

For the patients that we know, as David said, it's a subset of patients, the one that we're going through the hub or patients going through the hub and discontinuing 75% of them were late line, which gives a lot of confidence to us about the fact that, yes, the main patients will discontinue are clearly late line patients. If you go back to our clinical trial, the rate of discontinuation was very low, as you know, 6.5%, right? So this is really what we're going to see. We're going to see some of those late-line patients, unfortunately, as is expected in oncology, not responding very well to a third or fourth line of therapy. That's true in oncology. And what we've seen in our subset going through the hub is that those are the most discontinuation we see by far.

Understood. And then on the nonpivotal cohort SIGMA study that David, you just touched on, is there a threshold on ORR that you may have quantified or have in mind that would warrant that accelerated approval discussion? Sorry if I missed that.

I think that we've seen OR anywhere north of 20%. I mean this is a population, as you said, the biggest glioma drug in the world, vorasidenib has a 0% response rate in that population. So couldn't be lower, maybe, but certainly at 20% or higher, I think that would be extremely interesting.

The next question comes from the line of Greg Renza with Truist.

Congrats on the progress. David, just maybe on your current resource position. As you've commented on the current financial structure and also the path with the IBTRO

So you might recall that last year before we announced the Sagard Healthcare deal, we had said that at that point, we had enough cash to reach profitability. Well, since we made that statement, we raised $150 million with Sagard with another $50 million in debt. And then since then we've done a deal with Eisai, where we got another $60 million, and we'll have yet another $30 million upon European approval submission or approval next year. So we stand by that statement. We -- we have certainly far more cash than we need to get to profitability. Now if we do a significant business development deal that would certainly take some cash. But -- we're aware of the importance of getting to profitability without having to need additional financing. These are still difficult markets. I think that we, in general, we've been relatively conservative on that front. So we'll carefully weigh the upside of a deal. And certainly, any deal we do would have to be what we consider a good deal as we consider AnHeart, we think that was a great deal for us. So any further business would have to be a great deal for us. So we have to be -- we have to weigh the benefits and cons of using our cash and cutting into our runway to profitability. But we feel very, very confident that we'll get to profitability right now easily with what we have on hand. And we do believe that given what we have, we think that further business development is an important -- it's always been an important part of our company growth historically. And we think we will continue to look for opportunities that we think are particularly compelling for us, especially if they can capture some of the synergies that we already have within our company.

That's great. I appreciate that color. And maybe just one last one. If you could just comment on the DDC platform. I think I heard you mention maybe some updates into the year. Just maybe just remind us of your conviction on the platform as you invest at that area of the business?

So we are absolutely convinced that, that platform is real and has real potential. We -- that was a first-in-class compound. It's a first in history compound actually. So we learned a lot with 1511. And it wasn't that we didn't see any responses at all. We did see responses with 1511. It just weren't consistent enough for us to invest $100 million also in a Phase III study. We look at all our all our drug candidates as would this be worth spending $100 million on or should we make it better? And it's something you always have to balance in early-stage programs. So the answer for 1511 was probably not. And we learned enough to figure out how to make it better or to make a DDC better, and we are hard at work doing that. But we feel very confident that our DDC program will yield molecules that will go to the clinic and that we probably will take forward in development and we'll update you all hopefully by year-end this year.

The next question comes from the line of Yaron Werber with TD Securities.

Thank you very much, team, for the question. This is Steven on for Yaron. On the IBTRO

Sure. Let me take the first couple of questions, then I'll hand to Colleen. So -- so crizotinib is -- you still use a significant amount because it is pretty well tolerated. But as you know, crizotinib does not cross the blood-brain barrier. And when there were no options other than crizotinib, that would have been appropriate. Today, I would consider it about practice to use crizotinib in the first-line setting for -- when you don't really know which patient is going to go on to develop the CNS that way. First of all, 36% of them present with a brain met. But even if they don't -- we know that 50% of them will go on to get a brain met. I can't tell which the 1 of 2 is going to do that. And to give a drug that doesn't have any CNS coverage, in my opinion, as an oncologist is malpractice. I think that is inappropriate for patients. So I can't comment on how long crizotinib will be entrenched. I think that KOLs and patients appreciate the importance of CNS coverage. And I think that's part of our job and Colleen's team is -- that's one of our main messages. I think we have to continue to do that. So I can't tell you that crizotinib will go away. But I do think that over time, it is the absolutely wrong drug to use for this disease. In terms of engaging regulators to get preference in the first line setting, we do actually believe that our drug is differentiated. And we are looking at strategies to have that captured within the NCCN guidance. So on that, I would say stay tuned on that. But we are well aware of the difference in performance metrics of our drug against other drugs. So we think that IBTRO

Steven, I just want to elaborate a little bit more, so David spoke about -- the patients that we're receiving that have been pretreated, and obviously, progression toxicity that you just spoke to, brain-penetrant. So in addition to those patients, we're also looking to expand the market and you ask what else can we do? So I will tell you that it's our personal mission that we take it very personally that these patients that have ROS1-positive non-small cell lung cancer are going through their patient journey in the appropriate way. And 1 of those ways is to ensure that they're being tested before a treatment decision is made. So when we look at educational opportunities, we have several of them in this idea that patients are not only getting tissue, but liquid biopsies and I spoke about also earlier DNA testing being very, very important to understand the actionable mutations before a treatment decision is made. So in addition to us getting patients that are being switched off other TKIs, we are definitely growing the market and helping to educate more on the importance of understanding the entire picture before treatment decision is made.

Okay. And then on 868 and then the European approval?

So on the European side, we don't believe that any additional clinical trials will be needed, and we'll give you more details once the MA is submitted. On 868, there's been some interesting -- some interest in that compound. So I think we're looking at all our options.

The next question comes from the line of Silvan Tuerkcan with Citizens.

I just wanted to ask is the gross to net for the pricing stabilize at this point? And can you share where that's coming out? And if you have any idea where that will end up?

Yes. Thanks for your question, Silvan. So I mentioned during my presentation that we were a little bit above 25% for Q4 and that we were still expecting this to grow a little bit beyond that, to say exactly when it's going to stabilize is always a very difficult question because it all depends upon negotiations with payers, obviously. But yes, we think that we are in a very good place in terms of access, which is what we wanted. We really wanted to make sure that all patients that needed that access reported that's what we were. And we think that doing all of that will take us probably a little bit further up, but not so high. I give you much more detail than that. But yes, we're still going to increase that a little bit in the coming quarters.

There are no further questions waiting at this time. That will conclude today's call. I would now like to pass the conference back over to management team for closing.

Thanks so much. We want to thank you for all your support. Launches can be anxious. I think everyone has been looking at our numbers. We've gotten some feedback that some people might have been disappointed with the gap they perceived between the new patient starts and the revenue number. This is to be expected. As you know, in launches, especially in oncology and as an oncologist, I can tell you that late-line patients get started first. They're the ones that are out of options. The pool is already identified. This is a prevalent population. It's hard to find the new patients. So when you get those late-line patients, they're going to discontinue faster. I would say just be patient. It's all going to happen. We're very confident in this launch. We like the way things are going, and we think that we will get the first-line patients as long as those NPS numbers continue anywhere remotely in that ballpark. We know that we are running out of TKI experienced patients. The growth will be in first line. So I want to thank all of you for your continued support, and we look forward to updating you further on our next call.