Nuvation Bio Inc. (NUVB) Earnings Call Transcript & Summary

Right. And can you talk a little bit about your maybe commercial capabilities at this point? Is it the sales force? Is it rightsized at this point? And what are kind of the next focus point for the sales force in terms of getting in new hospitals or convincing some doctors that are not prescribing yet or just staying on top of the ones that are already prescribing?

Sure. So we look at where the ROS1 patients are. We believe that about 25% to 30% will be in academic centers and about 65% to 70% will be in the community. Right now, where we're finding our patients is the reverse of that. So we're finding most of our patients right now in academic centers because they tend to be early adopters and community takes a little longer. But what our sales force has been focused on is now trying to reverse that. And we're already seeing movement now towards increasing community use where the majority of patients are. It just takes a little bit longer in the community. We think the sales force is rightsized. We have 47 reps. But because of the way that community oncology is structured out, the vast majority of community practice, you don't really see mom-and-pop practices anymore like decades ago, but they're now aggregated into large community systems like OneOncology or Florida Cancer or U.S. Oncology. And because of that, it's a lot more efficient to reach those patients because now we go to these centers and we familiarize them with IBTROZI, and we can reach a lot more physicians with more efficiency than previously. So I think we aim to see the patients come from academic and community sources in accordance with their epidemiological split.

Great. And maybe for those not as familiar with your asset, could you just like review let's say, the label and the benefits it brings to the ROS1 indication with respect to the other TKIs that are out there?

Yes. So if you look at first-generation TKIs and ROS1, the PFS for entrectinib is16 months. For crizotinib, it's 19 months. The response rate for both those drugs is between 68% and 72%, so average of 70%. If you look at repotrectinib or AUGTYRO, the response rate is up to 79% and the PFS in the first-line is 36 months. But if you now look at IBTROZI, our overall response rate is now 89% with a PFS in the JCO publication of a year ago, which is still maturing at 46 months. So pretty clear that the benefits that we're seeing are substantial. In fact, there are actually no oncology drugs in any cancer that have shown a combined response rate and PFS as long as IBTROZI. So we think that's a pretty unique profile. And we're going to keep updating that label. We recently updated it last year, at the end of the year, showing now that duration of response has now moved up to 50 months, which now puts it among the very, very elite. Only LORBRENA or lorlatinib with a PFS of 60 months exceeds that. But we -- our data is still maturing. So we expect that to even -- that could even change further. But we are already in a very rarefied atmosphere in terms of our responses and durability of response. So we think that's pretty competitive. Also very importantly, if you look at our intracranial response rates, they're also very high, and that's important because ROS1 lung cancer is a disease that's going to get to your brain at least 86% of the time, 36% of the time, it starts in your brain at diagnosis, and then another 50% progressed in the brain as the first site of disease progression. So you need to have good central nervous system coverage. And if you look at our -- even in the second-line setting, if you look at our intracranial response rate of 66%, that's so far the highest seen of any ROS1 TKI. So we feel that the profile is pretty robust.

Yes. What's the kind of the impact or what could be the dynamics with generic crizotinib and entrectinib, like how would that...

Crizotinib doesn't get to the brain at all. So it's -- even though it used to be used in ROS1, it's actually not medically appropriate today. I guess if 86% of the time, you're going to get a brain met, to use a drug that doesn't even get in the brain, it's just not good medical practice. So we think crizotinib is a drug that should no longer be used in ROS1 disease because if you give it, you're just taking a gamble with whether or not you're going to get CNS coverage. And 86% of the time, you're going to lose because it's going to get to the brain. So I think that if you look at ROS1 treatments for ROS1 lung cancer, I think you need to pick drugs that have really durable responses because that means, by definition, you are working well against resistance mutations, and you need to use drugs that get to the brain that have high brain activity because that means that you're actually addressing the single biggest determinant of long-term survival, which is the development of brain mets.

And then I know you had some liver monitoring in the very beginning. Does that come up as any issue stopping uptake or?

Not at all. So LFT elevation is a paper issue and most patients don't even know they have it because they're not symptomatic. If you look at our 6 most common adverse events, LFT elevation were #1 and #2. And in spite of that, despite of being the 2 most common of our 6 most common adverse events out of 337 patients in our database, a number of patients who discontinued IBTROZI due to either elevation of AST or ALT was 1 patient. So 1 out of 337 is 0.3%. So that was our discontinuation rate for liver function test elevation, which we think is really the best among the TKIs that you've seen.

And then obviously, there are some eyeballs on Nuvalent who may launch a competitor later in the year in a later line and then maybe next year in earlier line. Can you just talk about how you view the competitiveness here versus potential profile?

Sure. So Nuvalent is applying for a second-line plus label. And their launch will be in second-line plus. If you look at the data they presented so far in the second-line setting, their response rate is 51%. But that 51% response rate is caveated by the fact that the ARROS-1 study excluded any secondary oncogenic driver mutation that wasn't ROS1. Our response rate in the second-line is 56%, so about 10% higher than Nuvalent's, but that 56% includes every oncogenic driver. So we made no exclusion. So we would argue that 56% with no exclusions beats 51% with exclusions. If you look at Nuvalent's confirmed response rate in the intracranial response rate in second-line setting, it's 45%. Again, excluding any secondary oncogenic drivers. Our intracranial response rate in second-line, including all drivers was 21 percentage points higher than that at 66%. We think that's pretty significant. If you look at the post entrectinib response rate of Nuvalent's drug, after you fail entrectinib, the response rate is 33%, ours is 80%. So we do think that there is a significant difference between the 2 drugs. We don't see -- we have not seen any metric so far where Nuvalent's drug has been able to match, much less exceed any metric of performance that we've seen. So we think that IBTROZI is a really efficacious drug. As I said, there are no cancer drugs in any indication that have matched our efficacy in the first-line setting. And by the way, we think the prevalence pool of second-line plus patients is probably in the range of 1,000. Well, we're getting 200-plus patients per quarter. By the time Nuvalent launches in the third quarter, we will have probably treated a majority of those patients and then moved upstream to first-line. So we think that we're really well positioned with the way this drug is working.

And to your point, Silvan. Just reminding everyone one more time. So we'll be launching first-line 2 years after this. That's a lot of time in our industry.

Yes. And you need to bring something better to the table, otherwise hard to penetrate.

Exactly.

Maybe, can you talk to us about your adjuvant plans? It's a very big population also.

Yes. So we are the only ROS1 TKI that's doing adjuvant. So that says several things. Number one, to go to the adjuvant setting where patients are generally asymptomatic, you have to have a drug that's really tolerable. And the fact that we've been encouraged by KOLs to do that, and we have now done it, again, speaks to the tolerability profile of our drug. As I said, if you look at our top 6 adverse events, our discontinuation rate for any of those is 0.3%. So pretty tolerable. So the reason the adjuvant space is important is because now you're talking about the farthest upstream you can go. When osimertinib did their adjuvant study, that led to them getting 100% market share. And we think that we're the only ROS1 TKI that's doing an adjuvant study. So we're -- even if anyone decides to try to get to the adjuvant space, they'll be significantly behind us. So we think that we're going to own that space and subsequently, we'll be the first drug used in the ROS1 lung cancer period.

Right. And maybe switching gears. I have many more questions on this, but it's a very interesting asset, and that's why we picked up coverage in the first place. But you also have safusidenib. If you could just talk about your progress here and with your IDH1 inhibitor.

Sure. So safu is a mutant IDH1 inhibitor. There's only one mutant IDH1 inhibitor approved in glioma. It's called vorasidenib or VORANIGO made by Servier. What's been striking about that compound is that in just their last quarter, they generated $258 million in sales in their fourth full quarter, which is remarkable. So that means that they're already on a $1 billion run rate for a drug that's only approved in 1 of the 4 parts of the glioma pie. So I mean divide the glioma pie into high risk -- high grade and low grade, it's about 50-50. But each of those segments can be divided further into high risk, low risk. So there's 4 pieces of that pie. Vorasidenib is only improved in one of those pieces, low risk, low grade. So if you look at vorasidenib's response rate in low risk, low grade, the response rate is 11%. And at 1 year, 23% of their patients had progressed. At 2 years, 41% of their patients had progressed. If you look at safusidenib's response rate and PFS in the same population, the low risk, low grade, instead of 11% response, we had a 44% response rate. Instead of 23% progression at 1 year, we had 4% progression at 1 year. Instead of 41% progression at 2 years, we had 12% progression in 2 years. So when we look at the low risk, low grade part of that pie, we think that safu's data is more robust. But importantly, vorasidenib is not approved in the other 3 pieces of the pie. So high risk, low grade; low risk, high grade; high risk, high grade. And we're doing a study called SIGMA that addresses all the other 3 pieces of that pie. So if that gets approved, we'll be the only drug approved in 3 of the 4 pieces of the pie. We're also doing a second study targeting grade 3 oligodendrogliomas because in that population, they all have measurable disease, but they can't -- because they live so long, in 12 to 14 years on average, they can't take radiation and chemo for those 12 to 14 years, so they need an oral therapy like safu. Because they have measurable disease, that trial was a response rate trial, and we think that potentially, if the response rate is very robust, a drug could be improved based on response rate alone in that population. We cite as precedent OJEMDA's approval in pediatric glioma for Day One in -- based on the response rate trial in 77 patients. So we are kicking off -- we have kicked off a 40-patient trial in the grade 3 oligodendroglioma patients. We will have a readout on that data set next year, but we'll start to see some data this year. If we start to see any response rates that are significantly higher than chemo, which is about 5% response rate, we think that warrants a discussion with the FDA to ask them what number of patients they would want to see to make this an approvable trial. As I said, OJEMDA was approved on 77 patients. So we had to make a wild guess, we think maybe 80 or so. We'll see what the FDA says. It depends on how robust the responses are. But we think there probably is a pathway to approval with response rate if the response rate is robust enough. So we're going to start to think about that toward the end of the year and we start to get our first patient data back.

Great. Well, thank you, David. Thank you, Philippe. Thanks for joining us today.

Well, thank you so much. Good to see you.

Thanks.