Afternoon, welcome to the H.C. Wainwright BioConnect Conference. I'm Robert Burns, a managing director and senior biotech analyst at H.C. Wainwright. I'm joined today by David Hung and Philippe Sauvage, the CEO and CFO of Nuvation Bio, respectively. Gentlemen, thank you for joining us today.
Thanks for having us.
Thanks, Robert.
For those who may be unfamiliar with Nuvation, give us a brief overview of the company and its pipeline?
We have three programs right now. IBTROZI is a best-in-class ROS1 inhibitor for a type of non-small cell lung cancer. That drug was approved in July last year. We've had 3 quarters of launch, which has been very successful. We have a second asset called safusidenib. It's an IDH1 inhibitor for brain tumors, and we believe that data also will make it a best-in-class drug. That's drug's in pivotal studies.
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. It, you know, it's coming up on almost a year since the approval of taletrectinib. I know that you're, you know, you present some updated pooled data from TRUST-I and TRUST-II. Talk to me a little bit about those updated results and how you see taletrectinib in the landscape and how it's differentiated relative to all its predecessors or any other compound that's in development for ROS1.
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 IO chemo, and the progression-free survival was about one year. First generation ROS1 TKIs had a PFS of about 16-18 months, but a response rate in the 70% range.
Repotrectinib was the first second generation agent, and it improved the response rate from 70% to about 79%. More importantly, the PFS doubled from about 1 and a half years to three years. Our recent updated AACR showed a response rate now of 90%, so by far the highest response rate among the ROS1 TKIs. 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.
Yeah.
There are no drugs today in oncology that have a combined 90% response rate and over 4-year DOR.
Yeah. No, it's quite impressive. You know, one of the things that 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 wanna get your thoughts on NVL-520. Obviously, you know, we got the second line data, and how that sort of stacks up against taletrectinib.
Sure. I think, first of all, I think the FDA's opinion is a lot more important than mine. The FDA granted IBTROZI, taletrectinib, breakthrough designation in the 1st and 2nd line setting, and the FDA granted Nuvalent's NVL-520 breakthrough designation in the 3rd line setting. That's the 1st important fact. The 2nd thing is that IBTROZI was granted priority review.
Yeah.
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.
Yeah.
They actually were downgraded to a standard review. 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 Nuvalent drug.
Yeah.
The second line response rate is 51%, excluding any concomitant oncogenic drivers.
Our second line response rate is 56%, including all oncogenic drivers.
Yeah.
It makes a much more real world, more difficult to treat population. More importantly, for a disease that will get to the brain 85% of the time, Nuvalent's intracranial response rate in the second line is 45%, excluding oncogenic drivers. Our intracranial response rate is 21 percentage points higher than that, 66%, including all drivers.
Yeah.
Right now we don't see a single metric where Nuvalent's drug can compare with the data we've generated, even in the second line plus.
Yeah. You know, from my perspective, taletrectinib is the end all be all as of right now within ROS1 positive. Why the hell are we seeing such a market cap discrepancy between Nuvation and Nuvalent from your perspective? Obviously I think the market caps should be inverted.
You know, they do have an ALK program. I think that people have high hopes for that program, we think that, you know, we can't really explain the ROS1 discrepancy. Even the ALK program, I think it's gonna be very difficult to beat lorlatinib.
Yeah
You know, lorlatinib has a 60-month PFS from the CROWN study, and they're gonna have seven-year CROWN readout at ASCO. I think that's gonna be a really, really hard drug to beat.
Yeah.
I can't answer your question, but you know, we're 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.
Yeah. You know, I wanna get your thoughts on this too, 'cause I know you're evaluating taletrectinib in the adjuvant setting.
Right? I wanna get your thoughts as to how you view that market opportunity in that particular setting, 'cause that's a pretty large market.
Yeah. Moving it upstream to the adjuvant setting will increase the market size another 30% on top of what we already have. What's really important is that we're actually the only ROS1 drug that's doing an adjuvant trial.
Yeah.
The reason it's hard to do an adjuvant trial is that you have to have a drug that's incredibly well-tolerated. 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 safety database, the number of patients who have discontinued our drug for any of those top six adverse events was 1 out of 337. 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 cases, because their tolerability is more difficult. I think that the adjuvant trial is another differentiator for IBTROZI because we'll 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 IBTROZI for ROS1 positive NSCLC patients that also have brain mets. Talk to me a little bit about how this provides a tailwind?
Yeah
For IBTROZI sales and revenue projections.
Yeah, the NCCN guidelines are important because, you know, prior to IBTROZI's, you know, 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.
Yeah.
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. About a year ago, the NCCN changed their guidelines and said that now if you have ROS1 lung cancer, IO is not only not an option, it's actually contraindicated.
Now you have to give a ROS1 agent for ROS1 disease. That just happened a year ago, which is why that market is still evolving as physicians change their practice.
Yeah.
That's a significant tailwind. It just takes a while to change practice, so we're seeing that already.
Okay.
The NCCN recently changed their guides again recently about a month and a half ago to now include IBTROZI in the CNS guidelines because of IBTROZI's, you know, really robust intracranial response rate, 66%. 66% is the highest intracranial response rate seen in ROS1 TKI so far.
We are now in the NCCN guidelines for CNS disease, and that's gonna be another deal.
Okay. With regard to modeling, you know, revenues for taletrectinib, can you discuss how investors should be thinking about their forecasts for this year in terms of revenue stacking? What do you forecast internally for peak taletrectinib sales? Give us a little thought about what that range, that window looks like for you guys.
If you look at the theoretical market maximum, there's about 3,000 new cases of ROS1 lung cancer every year in the U.S. alone. If you were to multiply 3,000 patients, new patients a year, this is the first line setting.
By the drug price, that's about $1 billion a year. Because of the duration of response is now over four years, that means that $1 billion in the first year goes to the second year and the third and fourth year, and everyone who starts in the second year goes to the third, the fourth, the fifth and sixth year, and goes on and on. By the fourth year, you have about revenue stacking of about $4 billion.
Yeah.
By DNA testing, that'll increase to another 30% beyond that to about $5 billion with RNA testing, as RNA is about 30% more sensitive than DNA.
Because of that revenue stacking and because you really see that in the first line setting, the percentage of first line patients is critical. If you look at our launch so far in 3 quarters, in our Q1 , we had 30% first line patients. In the Q2, we had 40% first line patients. Now in the Q3 , we've had over 50% first line patients.
Yeah.
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 stacking. We think that if that continues, the peak sales of the drug should be in the range of $4 billion-$5 billion if you capture that market.
Yeah.
Now that market will need to be addressed by testing. In the academic centers, that's about 100%.
Yeah.
In community settings, it's not quite as high. There's room for improvement in testing in the community setting, but we think the market opportunity is probably gonna 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 bit more than $80. Q1, $110. 35% quarter-over-quarter. 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.
That's right.
This is really the trend we are on. More and more first line patients, we know these patients will stay on drug for a very long time. The reason why, you know, the overall patient number quarter on can seem a little bit flattish is that because you have two phenomenon. You have first line patients growing, you have those later line patients going down.
They are going down because there are just not that many of them. We launched in a space which was incredibly dormant where nobody was promoting, not enough people were talking about this disease. The number of patients that were eligible for a second line was not that high.
Yeah
We are depleting that pool. 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, 3,000 a year. Yeah. No, that makes complete sense. Why don't we shift gears now to safusidenib. I really like this program a lot. You know, let's help frame what this program is and how it stacks up against some of the competitors.
Such as vorasidenib.
Sure.
Brain tumors that have IDH1 is a four-piece pie. The only drug approved today in IDH1 gliomas is vorasidenib.
It's only approved in one of the four pieces of the pie. 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. Vorasidenib is only approved in low risk, low-grade gliomas. Their response rate to get them that approval was 11%.
At two years, their progression rate was 41%. In the same piece of the pie, safusidenib has a 44% response rate, so 4x vorasidenib's 11%. At two years, instead of 41% progression, we had 12%.
In the low risk, low-grade part of the pie, we have data that we believe are hands down better than vorasidenib.
Yeah.
In the other three parts of the pie, vorasidenib in the high-grade setting has a 0% 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. We're doing two studies right now and planning a third. In a study called SIGMA, we're targeting three pieces of that four-piece pie.
Yeah.
Everything that's not the vorasidenib piece.
Okay.
That's a progression-free survival readout. Because it's a PFS, it takes a long time. It'll read out in 2029. We're doing a second study targeting half of the high-grade pie, which is the grade 3 oligodendrogliomas.
Because those patients all have measurable disease, the endpoint for that study is response rate.
Yeah.
It's a very fast readout. That study will read out next year.
Okay.
For the last part of the pie, we're contemplating a trial to target patients who have failed vorasidenib. If you look at Servier's numbers, they have treated over 5,000 people on vorasidenib, but I just mentioned a little bit ago that if you look at the Kaplan-Meier curve for vorasidenib, they have 23% progression at one year. 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.
I mean, you already got that's a 1,000 patients right there.
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 Chimerix, which got a brain drug approved based on 50 patients with an overall response rate, and Ojemda from day one getting approved on 77 patients with response rate, we think that a post-Vora response rate anywhere north of 20% in 50-80 patients could be enough for potential approval.
Okay. When are you thinking about initiating that sort of evaluation for that bucket of patients?
We're actually working on that right now.
Okay.
Yeah. We are already started on the first two, and we're finalizing the design on the last piece.
Yeah. For the grade 3 oligodendrogliomas, obviously, that date is coming in 2027.
That's an objective response rate readout. You know, is that something that you could then approach the FDA with? What do you think the benchmark needs to be? What do you think you need to hit in that patient population?
The response rate for chemotherapy, which is standard care.
Yeah
is single digits. We think anything over 20% is approvable.
Okay.
If you look at Chimerix, they were approved on 50 patients with a response rate of 21%.
Okay.
We think anything over 20% is approvable in somewhere between 50 to 80 patients.
Yeah
both the grade 3 oligodendroglioma 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.
Okay. 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?
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.
Yeah.
It's just looking for responses. I think that if we were to see, you know, any responses in that population, since there's nothing there at all.
Yeah
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 SAFU in my model. I'm not sure a lot of any other analysts do. I'm curious to get your consensus to the market opportunity here in each of those three buckets out of those four.
Yeah.
Can you talk to me a little bit about the market opportunity there?
The reason the market opportunity for IDH1 gliomas may very well be unprecedented, because there's almost no indications in oncology that have survivals that long.
Even high-grade patients with IDH1 live up to 6+ years.
Yeah.
Unlike high-grade, you know, GBM that's not IDH1, they don't live very long.
IDH1 tumors live much longer. Even high-grade astrocytomas can live 6+ years. If you talk about oligodendrogliomas, they can live 13, 14, 15 years. If you talk about low-grade glioma, they can live 20+ years.
Yeah.
You're talking about revenue stacking that could be literally four to 5x the IBTROZI 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 Nuvalent's market cap is what it is, and yours is less, especially with the revenue stacking potentials here.
Yeah. 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.
Yeah.
We've got a great pipeline. We feel, you know, very comfortable.
Yeah. Why don't we shift gears to your DDC platform? I, you know, I've always been fascinated by this platform. I know the story of how you came up with it, David. I love that story. 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 got from that asset, and what sort of update can we expect later this year with regard to the DDC platform?
Sure. ADCs are antibody drug conjugates. They work, they're some of the best drugs in the world are ADCs, but they're really big. We started Nuvation Bio based on a concept of drug-drug conjugates, which are much, much smaller than ADCs but have bispecific activity. We had taken a molecule called NUV-1511 into the clinic, and while we did see responses with it, before we invest $100 million-$150 million.
in a phase III study, we wanna take forward a drug that we think, you know, is the best shot we have.
Yeah
before making that kind of investment. We learned a lot in that program and thought there were ways to improve it. We actually have now made those changes. We will be announcing a new program later this year.
Okay. When you announce this program, is this gonna be you're gonna start the phase I relatively soon, or is this 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. Last question to you, Philippe, talk to me about the war chest and what the operational runway provides.
Well, I can start with the war chest. It's easy. 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, we are not looking for anything else right now from that perspective. We're feeling very, very confident about the level of cash. In terms of catalyst, I mean, obviously, continuous performance of IBTROZI.
We're incredibly encouraged by the ramp-up, especially this move towards first-line patients, plus recruitment on SAFU trials, which we think is gonna be rapid in many of them. I think that's the main point, 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.
Thanks, Robert.