Good afternoon. Welcome to the HCW BioConnect Conference. I'm Robert Burns, the Managing Director and Senior Biotech Analyst at HC Wayron, and I'm joined today by David Hong and Philippe Sauvage, the CEO and CFO of Nuvation Bio, respectively. Gentlemen, thank you for joining us today. Thanks for having us. Thanks, Robert. So, for those who may be unfamiliar with Nuvation, give us a brief overview of the company and its pipeline.
so we have three programs right now in trozi is a best-in-class Ross one inhibitor for a type of non small cell lung cancer that drug was approved in July last year we've had three quarters of launch which has been very successful we have a second acid called safra sitenib it's an IDH1 inhibitor for brain tumors and we believe that data also will make it a best-in-class drug that's drugs and pivotal studies and then we have a third platform our drug drug conjugate platform which we're going to be providing an update on later this
year awesome yeah I can't wait to speak about the DDC platform you know I'm a big fan of it but you know it's coming up in almost a year since the approval of teletrectinib and I know that you're you know you present some updated pool data from trust one and trust two so talk to me a little bit about those those updated results and how you see teletractib in the landscape and how it's differentiated relative to all its predecessors or any other compound that's in development for ROS1.
So ROS1 lung cancer is a particularly aggressive form of lung cancer and the problem with that disease is that the standard of care used to be IL chemo and the progression of your survival was about a year. First generation ROS1 TKIs had a PFS of about 16 to 18 months, but a response rate in the 70% range. Reprotracnib was the first second generation agent, and it improved the response rate from 70% to about 79%, but more importantly, the PFS doubled from about a year and a half to three years. Our recent updated AACR showed a response rate now of 90%, so by far the highest response rate among the Rossman TKIs, but most importantly, a duration of response now of 50 months. If you look at the number of times in the history of oncology that a drug has had a 90% response rate and a DOR of over four years, it's actually not happened. The only drug with a PFS in our range is lorlatinib, but with a lower response rate. So there are no drugs today in oncology that have a combined 90% response rate and over
four-year DOR. Yeah, no, it's quite impressive. You know, one of the things that I'm still trying to wrap my head, I've always been trying to wrap my head around this one, you know, a lot of people will cite one of the other competitor ROS1 drugs that's in development from Nuvalent. First, I want to get your thoughts on NVL 520. Obviously, you know, we got the second line data and how how that sort of stacks up against teletrectinib.
Sure, well I think, first of all, I think the FDA's opinion is a lot more important than mine. So the FDA granted Ibtrozi teletrectinib breakthrough designation in the first and second line setting and the FDA granted Nuvalens 520 breakthrough designation in the third line setting. So that's the first important fact. The second thing is that Ibtrozi was granted priority review. and we had a very, very fast approval. Nuvalent's drug, they applied for an RTOR, that was denied, and they did not get priority review. They actually were downgraded to a standard review. So I think that probably says a bit about what FDA's perspectives on the drug are. When you look at the nuvalent data, they only have really second-line data. There are no published data with the nuvalent drug. But the second-line response rate is 51 percent, excluding any concomitant oncogenic drivers. Our second-line response rate is 56 percent, including all oncogenic drivers. So it makes a much more real-world, more difficult to treat population. But more importantly, for a disease that will get to the brain 85 percent of the time, the valence intracranial response rate in the second line is 45 percent, excluding oncogenic drivers. our intracranial response rate is 21 percentage points higher than that, 66%, including all the drivers. So right now we don't see a single metric where a nuvalence drug can compare with the data we've generated, even in the second line plus.
Yeah, you know, from my perspective, talitrechnib is the end-all be-all as of right now within ROS1-positive. So why the hell are we seeing such a market cap discrepancy between nuvation and nuvalent from your perspective? Because obviously, I think the Marquette should be inverted.
You know, they do have an ALK program. I think that people have high hopes for that program. But we think that, you know, we can't really explain the Ross one discrepancy. And even the ALK program, I think it's going to be very difficult to beat Lulatinib. Lulatinib has a 60-month PFS from the Crown study, and they're going to have seven-year Crown readout at ASCO. So I think that's going to be a really, really hard drug to beat. So I can't answer your question, but we are very pleased with the results we've generated. We think Ibtrozi is clearly best in class, and our launch has gone extremely well. We think that's reflective of the profile of the drug.
I want to get your thoughts on this, too, because I know you're evaluating Teletrective in the adjuvant setting. So I want to get your thoughts as to how you view that market opportunity in that particular setting, because that's a pretty large market.
Yeah, so moving it upstream to the adjuvant setting will increase the market size another 30% on top of what we already have. And what's really important is that we were actually the only Ross One drug that's doing an adjuvant trial. The reason it's hard to do an adjuvant trial is that you have to have a drug that's incredibly well tolerated. And if you look at our top six adverse events, which are AST, ALT elevations, nausea, vomiting, diarrhea, and dizziness, out of 337 patients in our safe database, the number of patients who have discontinued our drug for any of those top six adverse events was one out of 337 so 0.3% discontinuation rate which is why it's being used in the adjuvant setting because you have to have an incredibly well tolerated drug there are no other drugs that have attempted to go to the adjuvant setting I think for many in many cases because their tolerability is more difficult so I think that the adjuvant trial is another differentiator for iptrose because will be the only drug upstream and that does increase the market opportunity another 30% beyond what we've already targeted.
Yeah, you know, I know the NCCN recently updated its guidelines to include IPTROZI for ROS1-positive NSCOC patients that also have brain mets. So talk to me a little bit about how this provides a tailwind for IPTROZI sales and revenue projections.
Yeah, so the NCCN guidelines are important because prior to IPTROZI's really unique data, I think that there was still a lot of IO chemo use in ROS1 lung cancer, even though IO's PFS, as I mentioned, is about a year. So up until 2024, though, the NCCN guidelines said if you had ROS1 disease, you had two options for treatment. One would be IO chemo, one would be a ROS1 agent. That all changed in the beginning of 2025. So about a year ago, the NCCN changed their guidelines and said that now if you have Rossman lung cancer, IO is not only not an option, it's actually contraindicated. And now you have to give a Rossman agent for Rossman disease. Now that just happened a year ago, which is why that market is still evolving as physicians change their practice. But that's a significant tailwind. But it just takes a while to change practice, so we're seeing that already. But the NCCN recently changed your guidance again recently, just about a month and a half ago, to now include IPTROZI in the CNS guidelines because of IPTROZI's really robust intracranial response rate, 66%, 66% is the highest intracranial response rate seen in ROS1 TKI so far. So we are now in the NCCN guidelines for CNS disease, and that's going to be another deal.
So with regard to modeling revenues for Tylotrectin, can you discuss how investors should be thinking about their forecasts for this year in terms of revenue stacking? And what do you forecast internally for peak Tylotrectin themselves? Give us a little thought about what that range, that window looks like for you guys.
So if you look at the theoretical market maximum, there's about 3,000 new cases of for hospital lung cancer every year in the United States alone. So if you were to multiply 3,000 patients, new patients a year, this is the first line setting, by the drug price, it's about a billion a year. But because the duration of response is now over four years, that means that billion dollars in the first year goes to the second year and the third and fourth year, and everyone Revenue starts in the second year, goes in the third, the fourth, the fifth, and the sixth year, and goes on and on. So by the fourth year, you have revenue stacking of about $4 billion. By DNA testing, that'll increase to another 30% beyond that, to about 5 billion with RNA testing, because RNA is about 30% more sensitive than DNA. So because of that revenue stacking, and because you really see that in the first line setting, the percentage of first line patients is critical. So if you look at our launch so far in three quarters, in our first quarter we had 30% first-line patients, but in the second quarter we had 40% first-line patients, and now in the third quarter we've had over 50% first-line patients. So that's the trend that's gonna be important, because as you see that first-line patient number grow, that's what contributes to the revenue stack, and we think that if that continues, the peak sales of the drug should be in the range of $4 to $5 billion if you capture that market. Now, that market will need to be addressed by testing. In the academic centers, that's about 100%, but in community settings, it's not quite as high. So there's room for improvement in testing in the community setting, but we think the market opportunity is probably going to be about $5 billion a year with RNA testing.
To go back to your point about short-term modeling, Robert, I think what's really important to note is that quarter-on, to David's point, we've been increasing our first-line patient number by 35%. Q3, roughly 60, Q4, roughly a bit more than 80, Q1, 110, so 35% quarter or quarter on. And if we keep increasing by 35% because of the extreme long durability of treatment in the first line, we get to consensus sales for the year, like roughly 130 million. If we manage to accelerate further, we beat that. So this is really the trend we are on. more and more first-line patients, and we know these patients will stay on drug for a very long time. The reason why the overall patient number quarter-on can seem a little bit flattish is because you have two phenomenon. You have first-line patients going, and you have those later-line patients going down. And they are going down because there are just not that many of them. We launched in a space which was incredibly dormant when nobody was promoting, not enough people were talking about this disease. So the number of patients that were eligible for a second-line was not that high, and we were depleting that pool. But what's really important and encouraging for us and for the modeling is really first-line patient building up Because that's where more and more patients are coming all the time three thousand a year. Yeah, no, that makes complete sense
Why don't we shift gears now divorce? Safucidinib. I really like this program a lot You know, but let's help let's help frame what this program is and how it stacks up against some of the competitors such as voracitinib.
So brain tumors that have IDH1 is a four-piece pie, and the only drug approved today in IDH1 gliomas is voracitinib. It's only approved in one of the four pieces of the pie.
So the pie is four parts. Half of them are low-grade, half of them are high-grade,
and of those, half of them are high-risk, half of them are low-risk. So voracitinib is only approved in low-risk, low-grade gliomas. Their response rate to get them that approval was 11%, and at two years their progression rate was 41%. In the same piece of the pie, Safflucitinib has a 44% response rate, so four times borosytonib is 11%. At two years, instead of 41% progression, we had 12%. So in the low-risk, low-grade part of the pie, we have data that we believe are hands down better than borosytonib. In the other three parts of the pie, borosinib in the high-grade setting has a zero percent response rate. Our response rate was 17%, but a third of those responses were complete responses, which means the tumor disappears. We've had a glioblastoma multiforme that's been gone for three and a half years, unheard of. We've had a high-grade oligodendroglioma gone for two years, unheard of. So we're doing two studies right now and planning a third. In a study called SGMA, we're targeting three pieces of that four-piece pie, everything that's not the borosytonib piece. And that's a progression-free survival readout. Because it's a PFS, it takes a long time. It will read out in 2029. We're doing a second study targeting half of the high-grade pie, which is the grade three oligodendrocleomas. And because those patients all have measurable disease, the endpoint for that study is response rate. It's a very fast readout. That study will read out next year. And then for the last part of the pie, we're contemplating a trial to target patients who have failed Vorocytinib. If you look at Servier's numbers, they have treated over 5,000 people on Vorocytinib, but I just mentioned a little bit ago that if you look at the Kaplan-Meyer curve for voracitinib, they have 23% progression at one year. So if they've treated 5,000 people, they started the launch 15 months ago, a significant number of those 5,000 patients will already start to fail now.
That's 1,000 patients right there.
So if we were to show responses in the post-vora setting, there are no approved agents post-vora. We think that's a potential accelerated approval. When we look at chimerics, which got a brain drug approved based on 50 patients with an overall response rate, and Ogemna from day one getting approved on 77 patients with response rate, we think that a post-vora response rate anywhere north of 20% in 50 to 80 patients could be enough for potential approval.
Okay, so when are you thinking about initiating that sort of evaluation for that bucket of patients?
So we're actually working on that right now. So we are already started on the first two, and we're finalizing the design on the last piece.
So for the great oligodendrocytomas, obviously that data's coming in 2027. That's an objective response rate readout. How are you thinking about, is that something that you could then approach the FDA with? And what do you think the benchmark needs to be? What do you think you need to hit in that patient population?
So the response rate for chemotherapy, which is standard care, is single digits. So we think anything over 20% is approvable. If you look at chimerics, they were approved on 50 patients with a response rate of 21%. So we think anything over 20% is approvable in somewhere between 50 to 80 patients. So both the grade 3 oligodendrocleoma study as well as the post-vora study are both response rate trials. that we think could be approved on somewhere between 50 to 80 patients.
You know, what's the sort of timeframe for that last bucket that you mentioned? Obviously, you're starting to get the planning ready for that post-Vora, you know, subpopulation. You know, what's that timeline look like then?
Well, because there's so many patients who've already gotten Vora and are already failing it, we think that the enrollment of that study will be quite rapid. And then it's just looking for responses. So I think that if we were to see, you know, any responses in that population, since there's nothing there at all, as an alternative, we would go straight to FDA and ask them, hey, what do you want to see in terms of size to make this an approval study?
Okay. You know, I don't currently include revenue projections for SAF in my model. I'm not sure a lot of any other analysts do. But I'm curious to get your senses of the market opportunity here in each of those three buckets out of those four. Can you talk to me a little bit about the market opportunity there?
So the reason the market opportunity for IDH1 gliomas may very well be unprecedented, because there's almost no indications of oncology that have survivals that long. Even high-grade patients with IDH1 live up to six-plus years. So unlike high-grade GBM, that's not IDH1. They don't live very long. But IDH1 tumors live much longer. So even high-grade astrocytomas can live six-plus years. If you look at oligodendrogliomas, they can live 13, 14, 15 years. If you talk about low-grade glioma, they can live 20-plus years. So you're talking about revenue stacking that could be literally four to five times the obtrose duration of response, which would be literally unprecedented.
Yeah, you know, I think when you put it in that context, it goes back to my point earlier. I don't know how New Zealand Smart Cap is what it is, and yours is less, especially with the revenue stacking potentials here.
We feel very comfortable where we are. We have a ton of cash. We have $535 million. That's well more than we need to get to profitability. We've got a commercial asset. That ramp is going well. We've got a great pipeline. So we feel very comfortable.
Why don't we shift gears to your DDC platform? I've always been fascinated by this platform. I know the story of how you came up with it, David. I love that story. but you know I know that you discontinued one of the earlier versions of you know one of the earlier assets out of this platform talk to me about the learnings that you that you got from that from that asset and what sort of update can we expect later this year with regard to the DDC platform so ADCs
are antibody drug conjugates there they work they're some of the best drugs in the world are ADCs but they're really big so we started the vision bio based on on a concept of drug-drug conjugates, which are much, much smaller than ADCs, but have bispecific activity. We had taken a molecule called 1511 in the clinic, and while we did see responses with it, before we invest $100 to $150 million in a phase re-study, we want to take forward a drug that we think is the best shot we have, before making that kind of investment. So we thought there was, we learned a lot in that program, and thought there were ways to improve it. So we actually have now made those changes, and we will be announcing a new program later this year.
Okay, and when you announce this program, is this gonna be, you're gonna start phase one relatively soon, or is this, it's still preclinical, you know?
We haven't said yet.
Okay, well I'm excited to learn what it's gonna be. I guess with the limited time that we have left, talk to me a little bit about the catalyst for this year, and then last question to you, Philippe. Talk to me about the War Chests, what the operational runway provides.
I can start with the War Chests, it's easy. So as David said, we have a bit more than 530 million. As we've said multiple times, that will be enough to drive us to profitability. So we are not looking for anything else right now from that perspective. And we're feeling very, very confident about the level of cash. In terms of catalyst, I mean, obviously, continuous performance of Iptrosi. We're incredibly encouraged by the ramp-up, especially this move towards first-line patients, plus our recruitment on SAFU trials, which we think is going to be rapid in many of them. I think that's the main point, and DDC at the end of the year.
Awesome. Well, gentlemen, thank you so much for joining us today. I really appreciate it.
Thanks so much, Robert.