All right. Well, good afternoon, everybody, and thank you once again for joining us for our Seventh Annual Oncology Innovation Summit. I'm Yaron Werber from the TD Cowen Biotech team. The Extel survey is now launched. If you do feel that the TD Cowen Biotech team has earned your support, please do consider voting for us for both large cap and small and mid cap. It's a great pleasure to moderate the next session with our Nuvation Bio. Really, we have two gentlemen that need no introduction. We have David Hung, Founder, President, and CEO, and Philippe Sauvage, who is the Chief Financial Officer. Team, thanks for joining us. Good to see you. Thanks for having us, Yaron. Lots to talk about. I mean, IBTROZI both commercially and then potentially to start even talking about other tumors that have ROS1 mutations. Let's maybe start on a commercial basis. As of Q1, now over 50% of patients using IBTROZI are in the frontline setting. I think you've noted on your conference call that the early trends in April continue to look encouraging. Can you give us maybe an update commercially on how usage is shaping up so far? Sure. Philippe, do you want to answer that? Yeah, I mean, what we've seen is very encouraging trends, right? This is something we really want to talk about more commercial launch. That's quarter-on-quarter, we had an increase of first-line patients. You know, Yaron, because of the incredible efficacy and duration of response of IBTROZI, first-line patients are really going to be the patients who are going to stay on drug for a very long time. This is really what is important for us for the long-term potential of IBTROZI. Quarter on, we see an increase of this patient number of about 35% a quarter. We think this is a trend we can maintain because the number of patients out there in need of IBTROZI is really high. It's still very much under-penetrated and still many potential for us to grow. These growth that we've seen in the first quarter of this year of more than 50% of our patients mean that it's growth of 35% again, quarter-on-quarter of our number of first-line patients. This is really what we see as the most encouraging recent data there. When you say, Philippe, when you say 35%, what do you mean, 35% quarter-over-quarter growth? Absolute number of first-line patients. Quarter- on- quarter, absolute number of first-line patients growing. It's not only about the share of it's really the absolute number growing quarter- on- quarter. Okay, you think that's sustainable from this point onwards? Again, if you think about the epidemiology, there are 750 patients a quarter that should be put on targeted therapy, and we only had 110 or so for IBTROZI in the first quarter. Still lots of room to grow there and keep that incredible good trend of first-line patients. The 750 is the newly diagnosed patients per quarter? That's the epidemiology, the number of patients out there that would need to be put on a TKI ROS1, yes. In the first-line setting. In the first-line setting. Got it. Do you have better line of sight into what's going on in the actual treatment setting? Given that most patients are not going through your program, right? It sounds like they're not going through Nuvation there. That's true. Most of the patients we know perfectly about are the ones that are going through NuvationConnect. This is a smaller share, which is why for a long time we were careful about not sharing too much information on first-line patients because we didn't want to say anything wrong. We've done a lot of work in the past few quarters understanding what was going on in the marketplace, looking at the patients we had in the hub, but also looking at all the other trends we can see from the feedback from our reps to doctors to some systems in which we have good insights of what's going on in the systems, to any data we can gather from IQVIA about line, et cetera. When you compile data like that and you all end up with the same number, you feel pretty confident about where you are. We really see this continuous growth of first-line trend, and we are very confident about it. Okay. What about the use of crizotinib? Do you have any sense as to what the dynamics are frontline there? We do see a decrease in crizotinib use. As you know, crizotinib has been one of the oldest TKIs out there, been around for the longest time, but doesn't get into the brain. We've been looking at now a number of healthcare systems. Some of the larger aggregators have shown some interesting trends. We've seen for the first time in one of our large aggregators a significant reduction in crizotinib use in the first-line setting to IBTROZI. I think that's a good trend, and we expect that to continue. Okay. You mentioned that this is going to be an ongoing sort of evolution quarter-over-quarter throughout the year. What drives that? Is it diagnosis, or is it really more uptake in the community setting? I think there are a couple of things that drive it. If there was one criticism of AnHeart, I would say there was probably not as much U.S. experience and familiarity with the drug as there could have been. We've now had three quarters to get the drug in front of physicians in the U.S., and that's been a great education for them. I think that they've gotten used to the tolerability profile, which is excellent. They've been impressed by the new changes in efficacy that we've just published and are updating in the sNDA of a DOR, duration of response of now 50 months, which is unprecedented. I think that with that increase in familiarity, these physicians are now changing their practice from using a new drug that they don't know about in the late-line setting to now using a drug that they've had experience with now in the front-line setting. We've seen scripts really change from primarily third-line or later in the very first quarter of launch, which was Q3, to now more than half in the first-line setting by the third quarter of launch, which is Q1. Got it. Okay. What do you think, by the end of the year, can you be at 75% more in front line of? No. Philippe said that we feel pretty comfortable. If you look at the growth in first-line patients on an absolute number, we went from about 60 in the third quarter to about 80 something in that range in the fourth quarter to about 110 in the third quarter. That's about 35% quarter-over-quarter growth, and we feel pretty comfortable that we should continue to do that. Philippe has made a comment on other calls that if we continue that rate alone with no acceleration. We should hit our consensus pretty easily. If we accelerate beyond that, we might be able to even beat consensus. I think that we're saying that this level of growth is something that we feel good about. We think it's sustainable, and that doesn't even take into account the gradual increase in testing, which we think is also happening in addition to changing practices due to familiarity of IBTROZI. I think that as all genetic testing increases for all lung cancer, I think that that's still a rising tide that will continue to float all boats. I think that in addition to the increase in familiarity with IBTROZI, we should further benefit by increased testing as well. Okay. Philippe, what is consensus now for the year for IBTROZI? It's around 130, between 130 and 140. As David Hung just said, if we keep increasing at that rate, our first-line patient will hit consensus. If we accelerate further, we'll go beyond that. We're feeling good about that number. I think to your previous question, it's not so much about proportion of patients. It's really about this first-line of patients, the first-line pool growing and growing and growing. Because we know there are other patients that are going to benefit from the longer time on IBTROZI, with this incredible duration of response, 15 months. This is really something that is important, that they will put on the best TKI in first-line so that they can stay on drug for as long as possible. Yeah. In terms of the other TKI, the branded TKI, are you still seeing them sort of competing in the market, or they're essentially ceded a share in the U.S. now? If you look at all the other TKIs, crizotinib use has probably started to decline, entrectinib use has already significantly declined. I would say that the closest drug to us in metrics of performance is probably repotrectinib. As we've just said, we are getting significant growth in first-line share in spite of repotrectinib. We think that the tolerability profile of IBTROZI compares favorably with repotrectinib. Frankly, if you even look at just the performance metrics, and you mentioned CNS control, in the second-line setting, IBTROZI's intracranial response rate is 66%, repotrectinib is 38%. I would say that just overall, IBTROZI has a very compelling efficacy as well as tolerability profile. Yeah. Okay. Zidesamtinib, e ventually I'm going to learn how to say the name of the drug, is expected to get approval in second-line setting in sort of early Q4. How do you think the competitive dynamic will work there? I think that, as Philippe has already said, we started off our launch in Q3 with the majority third-line or later patients. In Q4, we added second-line and later patients. In the three quarters since, we've captured a significant amount of the pre-treated market. We've started to grow first-line share, which we will be at least two years ahead of zidesamtinib for first-line launch. By the time they launch in second line, I think we will have captured a significant amount of the market. Also, we look forward to seeing their label. We have not yet seen a publication of zidesamtinib, and we'd like to see what their metrics really are as they would appear in a label. As an example, even though zidesamtinib presented unconfirmed responses in their publications, that's not acceptable in a label. Treatment-related adverse events, not acceptable in a label. We'd like to see the real data, confirmed responses, treatment-emergent adverse events, things that would appear in a label. We are not aware of any drug today that has any metrics in efficacy or tolerability that are close to IBTROZI. You're expecting really approval in second-line onwards, right? For zidesamtinib? Yeah. Yeah. Just to refresh your memory. The FDA gave them breakthrough designation in the third-line setting, but they're applying for a second-line approval. We received breakthrough designation in the first and second-line settings. On top of that, we got a priority review, and they did not. Again, for an agency that's seen all the data sets, they've certainly prioritized IBTROZI over zidesamtinib, and we expect them to have a late-line approval, and we expect their data to be inferior to ours. I think they're planning on filing for frontline, after the September 18th PDUFA. At that point, it's going to be a supplemental filing. What kind of a label do you think they can get in frontline? I think they have maybe 18 months to two years of follow-up so far, roughly? I think it just comes down to how good the data are, and we just haven't seen it. Yeah. Okay. In terms of formulary. For zidesamtinib, they will not have the level of maturity of data that we currently have, which we think is something that obviously we will have for a very, very long time, more maturity than they do. Also being two years ahead in the market is really, really important because. I mean, our response rate in the first-line setting is 90%. How much better can you get than that? Our duration of response in the first-line setting is 50 months. That's virtually unprecedented in all of oncology. I don't know how much better you can get than that. We feel really comfortable with our profile. I think this will be really, really hard to beat. There's a reason that we got first-line BTD and no one else did. I just think that the data should speak for itself, and we look forward to seeing it. Yeah. At ASCO, zidesamtinib is actually going to have data from other tumors, ROS1- positive other tumors. Is that something that you might be interested in doing studies as well? We actually had a small number of patients in our study, who had ROS1-driven cancers that were not lung cancer. They're more rare. In fact, we actually are currently treating a little girl with a ROS1 GBM, glioblastoma brain cancer, and she's had a great response to IBTROZI. Where we do see them, we think that IBTROZI is a great drug for ROS1, no matter what it drives, but those other cancers are far rarer than lung cancer. The main market for ROS1 is still lung cancer. Okay, that's not something that you're thinking about formally studying the drug in? I think everyone knows that our drug works great against the ROS1 fusion. As an example, when this little girl had a ROS1 brain cancer, they put her on IBTROZI, but that's not going to be the majority of our commercial opportunity. Yeah. Okay, for the audience, if you have questions, you can go ahead and put them right into the channel. Otherwise, you can go ahead and email them to me, and we're happy to take them on your behalf as well. Let's go to safusidenib and talk about, I guess there's definitely a lot going on, and that's a drug that's increasingly getting attraction and attention from investors. In terms of the IDH phase II and the non-enhancing low-grade glioma, now that you're controlling sort of the data, when do you think you might want to publish that data? We're going to try to publish everything we have, because I think the data are really compelling. We think that safusidenib is really an interesting drug because where vorasidenib is the only IDH1 drug approved today in brain tumors, it's only approved in one of the four pieces of the glioma pie, only in low-risk, low-grade. We have data in both low and high-grade brain tumors with IDH1 showing really significantly more robust responses and progression-free survival. We feel it's important to publish that, and we're going to do that. More importantly, we're now doing studies that are going to target all three pieces of that pie. Our SIGMA study will now target everything where vorasidenib isn't, which is high-grade, both low and high-risk, high-grade, as well as high-risk, low-grade tumors. That's three of the four pieces. We're doing a second study in the Grade 3 oligos, which are the lower-risk subset of the high-grade patients. Where vorasidenib has shown a 0% response rate in high-grade. Now we're even looking at designing another study in post-vorasidenib failures. That's particularly interesting because, as you know from vorasidenib's response rate and PFS, at one year, about 23% of vorasidenib patients progress in that low-risk, low-grade population, which means that they've been out for about 15, 16 months already, and the Servier has already said they've treated 5,500 patients. If a quarter of them are going to progress within a year, we think there could be 1,000 patients approaching failure right now. We think that the number of patients we would have to show responses in to potentially get us Accelerated Approval could number as low as 50 patients-80 patients. As you know, Chimerix got approved on response rate in 50 patients with a 21% response rate. Day One got accelerated approval based on 77 patients in pediatric glioma. We think that if we were to show responses in the post-vorasidenib setting of greater than 20% in 50 patients-80 patients, we think that's potentially a registerable study. We're now designing that study and think that out of the 1,000 or so post-vorasidenib failure patients, that should be happening within a year. We think that we could pretty easily get 50 patients-80 patients to assemble a package that would be pretty compelling to FDA. This is going to be in essentially adults at that point? Anything outside of pediatrics? Okay We're going to start in adults, for certain. Yeah. At that point, you'll use the same dose, the 250 mg BID? Correct. You mentioned the SIGMA study, which is essentially enrolling all three subtypes that Voranigo is not approved in, and then also a study that's going to be targeting that fourth indication where Voranigo is approved, right? Can you discuss that study, that second study? The SIGMA study is three of the four pieces that vorasidenib is not approved. Yeah. The second study is actually the Grade 3 oligodendroglioma study, which vorasidenib is also not approved. It's not approved in anything that has a high grade in it. That study is a response rate trial, and those patients can stay on drug for 12 years- 14+ years. It's a very significant commercial opportunity because of the revenue stacking that could occur. Because there's nothing approved in it, we think that's again, a trial that could be approved on as little as somewhere between 50 patients-80 patients. We cite OJEMDA with 77 patients approved on response rate only as a precedent for that. The third study is the study I mentioned that we're designing, which is a post-vorasidenib failure study. Their population is low risk, low grade. Right. We're talking about patients who have failed vorasidenib, for which there's absolutely nothing, a large market, a lot of patients out there right now because they've treated 5,500 patients, about a quarter of them will fail within a year. We think that we need 50 patients- 80 patients to get a pretty compelling package of sample. Right. Okay, yeah. Okay. Thanks for the clarification. That indication we talked about, the Grade 3 oligodendroglioma, that's actually the 40 patients as part of SIGMA? No, Yaron. It's actually part of SIGMA, but it's really a separate study in itself because it's specifically a pure population of Grade 3 oligos. While that trial is targeting 40 patients, which we should complete by next year, if we see responses in our first few patients, we would probably expand that to 80 patients instead of waiting for it to finish and then expanding, because, as I said, we just want to be ready to go with a package that we think FDA would find substantial enough to consider approval, and which we think at 80 patients would be larger than both the Chimerix and Day1 packages. Okay, got it. Okay. Right, it's sort of a part of SIGMA, but it's obviously a distinct protocol, a distinct study. Unlike SIGMA, which is a PFS readout, this Grade 3 is a response rate readout. Yeah, read out. Which is much faster. What's the bar there? Is the bar sort of 20%, or is it really 30%? Yeah. Chimerix got approved on 21%. We think north of 20%, if you look at the bar to beat, which is chemotherapy's response rate is in the single digits. We're talking 5%-8%. We think 20% easily beats that. We think anything north of 20%, like Chimerix did, is enough. Yeah. Okay. At that point, what's the durability? Does FDA want to see six months, or once you get a response, it's fairly durable anyway? I think we need to wait and see what FDA actually says, but I'm going to guess that there's nothing for these patients, it wouldn't be a really long time. Okay. You have 30 sites that you're opening or opened already, right? For this. We're opening more. Yeah, I think we are all about trying to move as fast now, and we would expect to have data from the Grade 3 oligodendroglioma study next year, and as well as we should have some data from the post vorasidenib study in at least some patients by next year as well. Got it. Okay. In terms of that you've signed up, I'm going to switch back to IBTROZI. You've signed the deal with Eisai. What's the next step in Europe now for IBTROZI? The next step in? In Europe. In Europe, David? Yeah. Yeah. We submitted for full approval in Europe. We expect to be reviewed in about nine months. That would be a normal timeline, Yaron. That would be early next year, somewhere Q1 or Q2 next year for an approval. It will be a typical European launch, how it works with country after country, starting with probably Nordics and Germany, as is usually the case. We've not discussed that yet with Eisai. We're still on the approval path. Got it. Remind us, what's the remaining milestones for approval for Eisai? We have a milestone for approval, yeah. Coming out time of approval of EUR 25 million, and that would be therefore early next year. That will reinforce even further our very solid balance sheet. We already have EUR 530 million, as you know. That will add to that. Okay. You potentially could draw down another EUR 50 million from Sagard, from your tranche with that? Yeah, we could. We've not made the decision yet. We'll wait to the last possible time to make sure that we have the right strategies there, but we can. Okay. In terms of SG&A, you've been kind of flattish between EUR 38 and EUR 40 a quarter. Is that sort of a good place where you'll remain for the time being? Obviously, we have a big acceleration of our commercial spend last year with the launch. Now we're getting more to a kind of stable situation from a launch perspective. We don't expect that to go up and down too much. There are always variabilities quarter- on- quarter, as you know. We don't expect that to be huge. Okay. Finally, any thoughts on business development and what kind of assets you're potentially looking at? Does it make sense to bring in other commercial assets, even if they're not huge, let's say, and they're fairly undervalued right now? I think it really just depends on the price we have to pay for them and how close they are to commercial. Clearly, later-stage assets are more attractive to us, but they're more costly. We have to balance what we think is a great deal and where the product fits into our pipeline to make a decision. We were really happy with the AnHeart acquisition. That was a great acquisition. We'd do that all over again. For us going forward, to move the needle for us, we would have to look at something that would be additive or synergistic with our IBTROZI commercial opportunity and had to be something within a reasonable price tag. Okay. There's so many assets in China. Does it make sense to go and bring something that was developed in China? No, we're looking at China. We have a big footprint there. We definitely are looking there, but we're looking everywhere because there are good assets everywhere. This is still a difficult financing environment. Many of these companies don't have a lot of options, there are a lot of assets we think that could be good opportunities for us. We're going to be patient and very disciplined about it. Yeah. All right. Well, David and Philippe, good to see you as always. Looking forward to seeing you at ASCO. Thanks for the interest. Thanks, Yaron. The next session starts in about four minutes. All right. Take care. Cheers.