Joining us for our next session at the RBC Healthcare Conference. Here we've got Nuvation represented by David Hung, their CEO, and Philippe Sauvage, their CFO. Thanks for being here.
Thanks for having us.
Thanks.
There's a lot going on at the company, but I figured maybe we'd start on the commercial side of the business first. IBTROZI achieved $18.5 million in first quarter revenues, about 200 new patient starts, and you talked about revenue stacking as a goal. I guess, what are your expectations for how you're going to be driving growth for the balance of the year?
If you look at, we've been out for three quarters, and if you look at new patient starts in each quarter, it has been about 200 new patient starts per quarter, which is more than the combined new patient starts of Augtyro and entrectinib combined. It is a good start. The number that we find most important is the percentage of first-line patients because the duration of response of first-line patients is over four years. Every patient who starts in the first-line setting would be expected to generate revenue for four years+ , about 4.2 years. If you look at third-line patients or fourth-line patients, they are on drug for a few months. When you look at new patient starts, while they appear to be roughly the same, about 200, it is because the late-line patients, which all oncology launches start with, are dropping off very quickly.
Sometimes if you're a fourth-line patient, you might last a month or two. They're going to drop. It's really only the 1st-line patients that really matter. If you look at our 1st-line patients' percentage among the new patient starts, in the first quarter it was 30%, in the second quarter it was 40%, in the third quarter it was over 50%. We're generating about 35% quarter-over-quarter growth in 1st-line patients, which I think is really, really exciting. If we can continue to do that, if we have no acceleration, we should still hit consensus for the year with just about $125 million-$130 million. If we accelerate beyond that, which we would expect to do at some point, we should beat consensus. I think we're comfortable with the number right now.
We do think that there are a couple of other ways that we will further increase revenue. Number one is testing. As you know, as recently as the beginning of 2025, the NCCN guidelines said there were two options to treat ROS1 lung cancer. One was IO chemo, the other was a ROS1 agent. On January 7th, 2025, so just a little over one year ago, that changed to say that not only can you not use IO chemo, but it's actually contraindicated, and now you have to use a ROS1 agent. That just changed a little over one year ago. Physician practice never changes overnight, but we think that is going to change and that's going to drive more ROS1 use because now the other main therapy that's been prescribed for decades is now contraindicated. That's number one.
Number two, I think that familiarity with IBTROZI is increasing. If there's one shortcoming of our AnHeart acquisition was that AnHeart had a very little U.S. presence. Even though they did a global study which included the U.S., Canada, Europe, they didn't have a ton of KOL exposure, and we now have three quarters of that. I think that physicians are getting familiar with IBTROZI. That should further drive revenue. I think there are really three things that will drive revenue. One is continued increase in first-line patients because if you look at our tolerability and our efficacy, there isn't anything close to us right now. We are over four years of duration of response. We are 90% response rate, which is the highest. Our tolerability is excellent.
If you look at our top six Adverse Events, out of 337 patients, one patient discontinued for any of the top six AEs. A really good profile. I think we're going to increase first-line share from familiarity, from increase in testing, and I think that's going to drive our revenue further.
Yeah, really helpful. There's a couple of things you touched on that I want to dive a little deeper on. The first is testing, as you just mentioned. Testing rates vary between academic centers, between community centers. At the same time, there's also new tests being developed.
Yeah
with mRNA. I guess, how much do you expect testing rates to improve? How do you think that's going to change the epidemiology of the disease?
Yeah.
Is there anything that you as a company can actually do to drive the testing rates?
I do think that it's going to change. A couple things. Number one, if you look at academic centers, they test about 100%. It's very, very high. If you look at community centers and some of the large community centers, we see testing rates 80%-90%. Some of the middle or smaller sized centers, we see testing rates as low as 40%-50%. Now there's a couple of reasons for that. One is just lack of awareness, and that we have to improve that. One of them is the fact that until a little over a year ago, the NCCN said that you have two options for ROS1 lung cancer. You can give IO chemo, which you don't have to get an NGS test for, or you can give a ROS1 agent, which you need an NGS test for.
If for those who opted for option 1, which was sanctioned, not only sanctioned, but recommended by NCCN, you wouldn't necessarily have to get an NGS test. Now that's changed because on January 7th of last year, that's now contraindicated. We think that testing will increase just by awareness, but also number two, by the fact that the NCCN guidelines have changed to contraindicate IO chemo. A third development is now we just got included in the new NCCN guidelines for CNS disease because of the brain activity of IBTROZI, and that's going to further push for this drug to be used, which will mandate a genetic testing. For terms of new tests, the RNA test is about 30% more sensitive for ROS1 fusions than the DNA test, and that was just introduced and approved about a year ago.
That's made it into NCCN guidelines, and it's going to be, again, a little while to get that to be mainstream, but we do think that DNA will ultimately shift to either DNA plus RNA or RNA, and that'll increase the epidemiology from 3,000 U.S. patients a year to about 4,000.
I think to your point, Leon, I need to add just a little bit. What's important to note is that of course, we're doing our part, but we are not alone. Lots of initiatives, NCCN guidelines, some state-sponsored initiative where it becomes mandatory to test, lots of companies out there. These are the testing companies or other companies with targeted oncologies pushing for tests. The whole field is changing. Everybody's pushing the same direction, which is the right direction for patients. If you think about it's really important because one of the reasons why we're stable, as was when we were talking about, is not because of our first-line growth, but because those late-line patients, they are not that many. Why are they not being that many? They were not tested appropriately. Many patients out there never benefited from a TKI.
That's really what needs to change and that's what everybody's pushing in the same direction. Technology is easier. Liquid biopsy is getting good. All kind of things are pushing in that direction, and we really believe it's going to change.
To Philippe's point about the national guidelines, Louisiana became the first state in the U.S. to now require NGS testing if you have lung cancer because the outcome of patients with a genetic mutation is so much different than one who doesn't have one. It's actually required by law in Louisiana. Dozens of states have legislation before them mandating the same thing. It's a national movement that is going to change genetic testing.
You also mentioned CNS activity. I guess, is that a differentiating feature of IBTROZI? I guess how important is that going forward? Is that something you sort of leverage in any of your commercial conversations, especially just given the rate of metastasis?
That's a really good question. I think it's a huge differentiator, and the reason is ROS1 lung cancer either starts in the brain or goes to the brain. It's going to happen. 36% of the time when a patient is diagnosed, they already have a brain met, and then another 50% of patients, when they progress, they're going to progress in the brain as the first site of disease progression. That's already 86% of patients. That's the vast majority. If you look at the crizotinib, the first-generation TKI, it doesn't even get in the brain. If you look at entrectinib, one of the other first-generation TKIs, it's progression-free survival 16 months, a third of what we're talking about. Repotrectinib is the most effective second-generation agent, but its intracranial response rate is 38%. Ours is 66%. Again, not even close.
If you look at Nuvalent, which is trying to get a second-line approval this September, their intracranial response rate is 45%, excluding any oncogenic driver. Again, our response rate in the brain is 66%, including all drivers, so much more reflective of a real-world situation. There isn't any agent that has CNS activity that's close to ours.
You mentioned one of the competitors, and I guess I have to follow up on that. How are you thinking about how the market might evolve as new agents enter? You've talked a little bit about the KOL feedback.
Yeah.
I guess what is it that they're looking for in a drug? Is it the efficacy? Is it the safety? I guess, how do you play to your strengths as the market gets more competitive?
The first point I'll make is that efficacy and safety are indistinguishable in the sense that the single greatest safety risk to a patient is progression, but by far. Whether you talk about dizziness or anything, GI side effects, the worst thing that can happen to a patient is progression. If you look at our duration of response, how long do patients on IBTROZI stay on drug? How long do they respond to our drug? It's over four years. The second closest drug is about a year and a half shorter than that. Just right off the top, I'm going to say efficacy and safety are indistinguishable. Whoever lasts the longest on a drug, it's the drug that's the safest. Because once you have a brain met, once you have progression, you're not going to do well.
On top of that, if you look at our safety profile, out of the top six Adverse Events, which are AST elevation, ALT elevation, nausea, vomiting, diarrhea, and dizziness, in that order. Out of 337 patients in our safe database, one patient discontinued for any of those six events. That's 0.3% discontinuation. From tolerability standpoint, there isn't a drug that's close to that. If you look at our adjuvant study, we are the only company that's doing an adjuvant study in ROS1 because you have to have a drug that can be taken for years. Our drug is tolerable enough that we are actually doing that study. The best testament to tolerability is your duration of response. Our median duration of response is over four years, which means patients are taking that drug for over four years. If it were intolerable, they wouldn't get close to that.
They're taking it for 4-plus years. This drug is highly tolerable, but it also has a 90% response rate and a 50-month duration of response. There are no drugs in that space that have anything close to those metrics.
Got it. There's a lot more we could talk about on taletrectinib, but I want to make sure we also have some time to talk about safusidenib, which is a program that I'm really excited about. Maybe we'll pivot there. I guess, maybe to set the groundwork, you've recently shared additional data on that program, including data that was at one point owned by one of your partners.
Yeah.
I guess, just to level set, how do you compare what you're seeing there with the approved agent in glioma?
Yeah. IDH1 gliomas right now are a pie composed of four parts. Half the pie is low-grade, half the pie is high-grade. Within each of those sides, roughly half of them are high risk, and the other are low risk. vorasidenib is approved in one of the four pieces. It's approved in low risk, low-grade glioma. If you look at their response rate to get them their approval in low risk, low-grade glioma, it was 11%. At one year, they had 23% progression. At two years, they had 41% progression. If you look at our data in the identical subset of patients, low risk, low grade, instead of 11% response rate, we had 44%. Instead of 23% progression at one year, we had 4%. Instead of 41% progression at two years, we had 12%.
When we look at low risk, low-grade glioma, we think that our safusidenib data are hands down better data. If you look at the high-grade part of the pie, vorasidenib's response rate is zero. If you look at our response rate with safusidenib in high-grade glioma, it was 17%, but a third of those were complete responses. Complete response means the tumor has disappeared. One of the tumors that disappeared in one of our patients was a GBM, glioblastoma, the most difficult of all tumors. That tumor's been gone for three and a half years. We have a second high-grade response, a Grade 3 oligodendroglioma, which has been gone for about two years. Again, responses that we just don't see with vorasidenib. We're doing two studies and contemplating a third. The SIGMA study will take three of the four pieces of the pie where VORANIGO isn't.
VORANIGO's in that low risk, low-grade piece of the pie, where SIGMA will target everything else. That's a PFS study, so it's longer. It reads out in 2029. We're doing a second study, which is a Grade 3 oligodendroglioma study, which is part of the high-grade pie where VORANIGO has no response. Because Grade 3 oligodendroglioma patients all have measurable disease, unlike the SIGMA study, the endpoint of this study is response rate. There is nothing approved there. We think that if we see anything north of 20% response, that is a potentially approvable pathway. If we look at Chimerix, they were approved on 50 patients with a 21% response rate. If you look at agenda, they were approved on 77 patients with response rate.
We think that somewhere between 50 to 80 patients with a response rate over 20% potentially gets us approved in Grade 3 oligodendroglioma. That's high risk. We're contemplating and designing a third study. We look at the VORANIGO low risk, low-grade market. I just mentioned that if you look at VORANIGO's data, 23% of their patients treated with VORANIGO progress within one year. Well, Servier has announced that they've treated more than 5,000 patients since launch with VORANIGO. If 23% of them progress within a year, around 1,250 patients will progress around 12 months out. Servier launched that drug 15 months ago. We need somewhere between 50 to 80 patients showing a response rate post-VORANIGO, we think, to get approval. We're designing that study now. We think that that's a quick response rate readout.
We think anything north of 20% in somewhere between 50-80 patients gets us a conversation with FDA to discuss accelerated approval. Those are the three studies. Two of the three studies we're talking about are response rate trials. The Grade 3 oligodendroglioma study reads out next year. Potentially, the VORANIGO study should be quite fast because there should be 1,000 patients or so who are failing VORANIGO out of the 5,000. If 23% fail within a year, there should be 1,000 to pick from, and we need 50-80. I think that's going to be a quick enrollment and a relatively quick readout. Two of the three studies will have response rate readouts probably within a year or so. The SIGMA study will be a confirmatory study with PFS that will read out in 2029.
Got it. When people think about brain cancer, they don't necessarily think it's a large opportunity, yet you just mentioned that in about a year, Servier treated 5,000 patients.
Yeah.
Right? Can you help us maybe better understand what the size of this opportunity actually is?
The reason for that is because the incidence of IDH1 brain cancer is about the same as ROS1, about 2,500 patients a year. Unlike ROS1, they live even longer. High-grade IDH gliomas live 6+ years on the high end. Grade 3 oligos can live 12-14 years. Low-grade gliomas can live 20+ years. We're talking about a prevalence pool that's in the tens of thousands of patients. VORA is showing that, because in their last quarter, they generated $312 million in one quarter. They're already well over a billion-dollar run rate because there's such a large prevalence pool, and they're going to be on drug for years. Now, if you look at the VORA data in low-grade, at two years, 41% of their patients progressed. If you look at our data, 12% have progressed at two years.
If you just make it linear, which it probably isn't even linear, you can see that we're talking about a long, many, many years on therapy. Here's another fact. If you look at our recent Daiichi data, out of 27 patients that Daiichi treated in the study, 12 of them are still on drug at five years, but not all of those 12 were even progressers or responders. What that means is that you don't even have to have a response for patients to be kept on drug, because non-progression for a disease that invariably progresses and kills you is a good thing. Even though we have a 44% response rate, so you would think that 44% of people would be on drug.
The point of the Daiichi study that we just disclosed at five years means that beyond 44%, those who don't progress, even if they didn't respond, could be kept on drug. Now you're talking about a really large number of that prevalence pool of tens of thousands of patients. So the commercial opportunity of safusidenib is multiple IBTROZI. IBTROZI i s big. We think at the peak, it should be $4 billion-$5 billion, but if you look at VORA, it's already well over $1 billion in its fifth quarter. We think that's going to be a multibillion-dollar drug, and we think safu should do better than that.
I guess you talked about the excitement and the potential enroll quickly, and I guess the SIGMA trial is in progress. Can you talk about what you're hearing from investigators and how sort of the ClinOps execution there is going?
The SIGMA trial is exactly on track. Our predictions on enrollment rate were spot on. We've said that the latest we'll read that out is 2029, we'll stand by that. Interestingly, we're actually getting a lot of calls from KOLs and patients to see whether or not they can put their lower risk, low-grade patients on safu instead of VORANIGO, even though we're not approved. They've seen the data, and they think that given our response rate in both low and high-grade, they've inquired whether or not they can get their patients on safu instead. I think that's a pretty good marker of interest in safu.
The unmet need is immense. The patients are out there. They are all identified. We don't have the same problem as we have in ROS1, and we have a very, very good drug. I mean, so far the recruitment in the trials have been very positive, and we think it's going to continue.
You've laid out that the data looks pretty impressive. I guess, what do we know about why safu might be more potent than some of the other inhibitors? I mean, is there some secret sauce or special thing to the mechanism here?
When we look at the Adverse Events, what we've pointed out is that of the top seven Adverse Events of safusidenib, even though they're almost all Grade 1, five of the seven are immune type AEs, things like skin hyperpigmentation. You just don't see that very often. Arthritis and rash, these are things that are associated with many known autoimmune disorders. If you look at the response rate of safu, often it takes a few months to kick in, and when you get a response, it lasts for a really long time. It's very reminiscent of IO. We've been doing some preclinical experiments, and we have reasons to believe that safu does have an immune component to its activity that's perhaps even independent of just IDH1. We are further dissecting that. We think that our clinical profile speaks for itself.
The efficacy is very different. The safety is very different. We think that this drug is just an unusually effective drug for this disorder. We are pretty confident that we're going to see pretty robust effects in our trials.
Got it. I wanted to just touch on sort of the market one more time. You've segmented the market into four pieces, right? There's sort of the high risk, high-grade patients that don't have any options right now, but presumably, they won't necessarily stay on drug for a while. I guess how do you think about the component in each piece of the pie, not just in terms of the patient number, but how they might ultimately contribute to the revenue opportunity and sort of the timing as those come online?
High risk, high grade, unlike non-IDH1 mutated tumors, these patients live much longer. Even the high risk, high grade can live 6+ years, unlike GBM that's non-IDH1 mutated. Those patients can live six months. Every piece of the glioma pie could live 6+ years in the highest risk subset of high grade, up to 20+ years in the low risk subset of low grade. It's really a long survival in a large prevalence population. We think that the patients will be on drug for potentially a decade or longer on average.
Got it. We've got just a minute left. Maybe I'll end with a bigger picture strategy question. You guys are commercializing IBTROZI, working on safusidenib. You've also historically been active on the BD front. I guess, how do you think about all these potential capital commitments?
We have $535 million right now, or we have enough to get to profitability. The launch is going well. We're going to focus on IBTROZI and really make sure we stick the launch and make sure that we continue to grow first line. We're going to get safu through clinical trials as quickly as possible. We think especially those two response rate trials will give us a relatively soon readout. I mean, we're talking about 2027, next year. The PFS study could be a confirmatory study. We're going to announce a new DDC program later this year. We think that's pretty exciting. We're capitalized to do all of it. Of course, we also always look at BD. I think that there are a lot of really interesting opportunities out there. Of course, we have to pay the right price for it.
We're going to be very selective and disciplined about that. If we see an opportunity that is clearly as value-generating as the AnHeart acquisition was, which worked out well for us, I think we'd do that in a heartbeat. We're going to just be very disciplined and careful about our BD, but it is certainly in our future.
Yeah. We have the resource to do all of the above and beyond.
Great. Excellent. That's all the time we have. Really appreciated speaking to you guys today.
Thanks much.
Thank you.