Thank you for joining us on the next great session here at the 2024 Jefferies London Global Healthcare Conference. I have the great pleasure of introducing the CEO of Nuvation Bio, Dr. David Hung, up to give a presentation. And if there's any questions after that, I'm sure there'll be some great dialogue. Thank you. Thanks, Mike, and thank you all for coming. So, Nuvation Bio is a late-stage oncology company. We have multiple drugs that are pipelined for, to be exact, two late-stage, two early-stage. Our first asset is a drug called taletrectinib. It's a next-generation, potentially best-in-class ROS1 inhibitor. And we just submitted a line-agnostic NDA in October and anticipate acceptance of that NDA later this year and a commercial launch in mid-2025. Safusidenib is also a potentially best-in-class mutant IDH1 inhibitor that's demonstrated interesting results in phase II in IDH1-mutated glioma. And we're in the process of looking at what a pivotal study might look like. 1511 is our first drug-drug conjugate candidate. It's in a phase I study. And NUV-868 is a BD2-selective BET inhibitor that has just completed phase one-two. We have a healthy cash balance of about $549 million. As I mentioned earlier, we anticipate an NDA acceptance for taletrectinib around year-end. And we anticipate being a commercial-stage organization by mid-next year. As I said, we had four programs, two late-stage, two early-stage. The first one I'll focus on is taletrectinib. This is a drug that we acquired when we acquired AnHeart Therapeutics in April of this year. This is a drug that has breakthrough designation in both first- and second-line in both the U.S. and China. And I'll talk a little bit about the efficacy and safety profile of this drug, which we believe are best-in-class. AnHeart acquired this asset through Daiichi Sankyo in 2018. And we maintain global rights, except in China and Japan, where the rights have been out-licensed. Taletrectinib has been evaluated in two pivotal studies, including more than 300 patients in total, with results supporting breakthrough designations in both the U.S. and China. Our data set of TRUST-I and TRUST-II, which are the names of the two pivotal studies, includes 337 patients, which is one of the largest ROS1 available patient populations studied thus far. The patients have been studied in both the first line TKI naive setting and the second line TKI pretreated setting. If you look at our data here, I can summarize things from right to left. First-generation TKIs for ROS1 lung cancer include entrectinib and crizotinib. If you look at the highlighted yellow figures, the response rate of entrectinib is about 68% and crizotinib about 72%. If you look at the progression-free survival, entrectinib is about 16 months and crizotinib is about 19 months. The first approved second-generation TKI for ROS1 non-small cell lung cancer is repotrectinib. You can see that there was an improvement in overall response rate from around 70% to 79% and an improvement in median PFS from about a year and a half to 36 months or three years. If you look at the far left, taletrectinib's response rate is 89%. I can tell you that that 89% is comfortably above the upper bound of the 95% confidence interval for repotrectinib's 79%. We can actually say this is a significantly improved overall response rate. Our median PFS now is 46 months, so significantly longer than even repotrectinib's 36 months. To put this profile in just some context, in the history of oncology drugs, there are few agents that have demonstrated response rates of nearly 90% and PFSs of nearly four years. Just to put that in perspective, Xtandi from Medivation, the PFS of Xtandi in the PREVAIL study was 20 months. And today, Xtandi is the largest prostate cancer drug in the world with $6 billion a year in sales. If you look at osimertinib, the best drug in the world for EGFR-positive lung cancer, the FLAURA study showed a PFS of 19 months. So taletrectinib's 46-month PFS puts it in really an elite group of drugs that have been able to show response rates and durations of response this high. To put it in further perspective, if you take a drug like crizotinib or entrectinib, which are first-generation TKIs, as I mentioned earlier, you get PFS about somewhere between 16 and 19 months. And entrectinib is the only brain-penetrant first-generation ROS1 inhibitor. So if you fail entrectinib and crizotinib and then go on to repotrectinib, the only approved second-generation TKI for ROS1, you get an initial 9 months of PFS. So if you add up 16 plus 9 or 19 plus 9, you get somewhere about between 25 and 28 months of PFS by combining the existing drugs for the treatment of ROS1-positive non-small cell lung cancer. By contrast, for the data that we've just presented at ESMO with the TRUST-I and TRUST-II data set, taletrectinib would give you nearly 21 months longer PFS if used in the first-line setting. We believe that's a compelling argument for why clinicians will opt to use this drug. If you look at the market size for ROS1 non-small cell lung cancer, it is not a small market, even though the actual number of patients is about 3,000 per year in the United States. If you look at the estimated patient populations, as you can see here on the screen, in the U.S., it's about 3,000 patients per year. Given the long PFS that we've demonstrated in the TRUST-I and TRUST-II trials, how would that play out? Every year, if you have 3,000 new patients in year one, if you multiply 3,000 times the current selling price of repotrectinib, which is about $350,000 a year, that would be about a billion dollars. That would happen every year because the incidence of ROS1-positive non-small cell lung cancer is about 3,000 patients per year. Every year, you get about a billion dollars. In year two, you get an additional billion because your patients will continue through year two, and they'll continue through year three, and they'll continue through most of year four. So if you look at the stacking of revenue you get with a PFS of 46 months, it totals about almost $4 billion a year by year four. So even though there are only 3,000 ROS1 patients alone in the United States, this is not an incidental story. With the PFS this long, it becomes a prevalent story. And if you look at all the drugs in history which have had really robust sustained revenue, Gleevec or Revlimid, these are drugs with fairly long PFSs. And we think that this turns this into a prevalent story and a pretty sizable market opportunity. If you look at the second-line setting, taletrectinib also has, again, the highest objective response rate and median PFS of any ROS1 inhibitor in the second-line setting. If you look at the only approved ROS1 TKI in the second-line setting, repotrectinib, the response rate is 38%. Taletrectinib is 56%. If you look at the PFS of repotrectinib, it's nine months, as I mentioned earlier. Taletrectinib is 10 months. If you look at the intracranial response rate, repotrectinib has a 38% intracranial response rate. Ours is 66%, so significantly better, and that's particularly important because as patients become longer and longer in their disease, CNS metastases start to play an increasingly important role and are an increasing limitation of their survival. So the intracranial response rate is important. If you look at zidesamtinib, which is Nuvalent's drug, NVL-520, there are very, very few patients with data in that indication so far. Nuvalent has only presented data on 20 patients so far in the ARROS-1 study, and if you look at Nuvalent's response rate after crizotinib and entrectinib failure, it's 53%. Ours is 56%. If you look at their response rate following repotrectinib failure, it's 0%. It's also noteworthy that in the ARROS-1 study, the post-entrectinib response rate for NVL-520 was about 15%. Ours was about 80%. If you look at the intracranial response rate for NVL-520, it's 50%. Again, ours is 66%. As the data stand currently today, there are no metrics really upon which any other drug can claim superiority to taletrectinib. We believe that our data show best-in-class metrics on virtually every measure of efficacy in either the first or the second-line setting. If you look at the safety profile, taletrectinib is also very well tolerated. The most common adverse event seen with taletrectinib is elevation of liver function tests. These are very common with many TKIs, and oncologists are very used to dealing with elevation of liver function tests. The way you manage that is either dose modification of some sort, either dose interruptions or dose reductions. If you look at the far left, the green bars are the dose interruptions and reductions with taletrectinib. And you can still see they're lower than the dose interruptions with repotrectinib or entrectinib. And the bottom line is if a drug is tolerable, the discontinuation rate of that drug will be low. If the drug is intolerable, it will be high. And taletrectinib's discontinuation rate of 7% ranks it among the lowest of all the ROS1 TKIs, nearly half the discontinuation rate of crizotinib. If you look at the right side of this slide, one of the major differentiators between taletrectinib and repotrectinib is the CNS toxicity rate. Repotrectinib has severe frequent CNS toxicity events, 65% dizziness. Taletrectinib has less than a third of that, and it is also primarily grade 1, so a much more tolerable overall profile, especially in the CNS. We are the only ROS1 inhibitor currently in development to have been granted breakthrough designation by the FDA in both the first and second-line settings. We have filed the NDA in October. We anticipate acceptance later this year. We'll be launching this drug in the United States and anticipate partnering Europe. And the license agreements that we have provide for royalties from Innovent, from our China launch, and Nippon Kayaku in our Japanese launch. Our second drug is safusidenib. This is a drug that targets mutant IDH1, which is a glioma target. This is a large unmet need. As you know, gliomas are brain tumors that have very, very few treatment options. High-grade glioma, most of you know as glioblastoma multiforme in the old nomenclature, an almost invariably fatal tumor, which there are very, very few treatment options for. IDH1 is a validated target of vorasidenib. The Agios drug was just approved for the treatment of low-grade glioma, grade 2 glioma, in August. And based on that approval, Agios struck a nearly billion-dollar deal, a $905 million payment from Royalty Pharma for a 15% royalty on the U.S. vorasidenib sales. I'm going to go through our profile of efficacy and why we believe our drug is well positioned against vorasidenib. And we have global rights to this drug. This drug we got also from AnHeart, and they in-licensed it from Daiichi Sankyo in 2020. And Daiichi Sankyo retains Japanese rights and is also still running Japanese studies. This is a significantly larger market than the ROS1 non-small cell lung cancer market. About two-thirds of IDH1 mutant gliomas are low-grade or grade 2. About one-third are high-grade or grade 3 or 4. The current data set for safusidenib approaches about 100 patients. As I mentioned earlier, this is a validated target. Royalty Pharma paid Agios $905 million for a 15% U.S. royalty on vorasidenib sales. If you look at vorasidenib's response rate in low-grade glioma, also called non-enhancing glioma on the right, you can see that in their phase II study, vorasidenib's response rate was 18%. In their pivotal phase III INDIGO trial, that grade 2 objective response rate was 11%, 10.7%. In the data that we've presented on the left in our first study, the response rate in low-grade glioma in the gray bar was nearly three times the INDIGO response rate at 33%. We're going to be presenting further data on safusidenib next year from Daiichi Sankyo, which will show again that safusidenib has a very favorable profile compared to vorasidenib. If you look at the response rate of vorasidenib in high-grade glioma, you can see on the right it's 0%. And if you look at the left in the green bar, safusidenib has a 17% objective response rate in high-grade glioma. However, if you divide that out a little further and look at the green bar, 6% of the 17% objective responses in high-grade glioma were complete responses. Complete response means the tumor has disappeared. And notably, if you look at the title of those two complete responses, one of them in a GBM, a grade 4 astrocytoma as it's now called, the tumor disappeared and is still gone 174 weeks later and still going. So we're waiting for the next data update, but that's more than three years. A second patient with a high-grade glioma, this time an oligodendroglioma, has also had a complete response. It's 95 weeks out with, again, no reappearance of the tumor so far. We're still waiting for additional data cuts. We believe these data are striking. We're not aware of any other drugs that have this profile. We are very enthusiastic about this drug. I think it offers potentially significant benefits even over vorasidenib. Our third program is our drug-drug conjugate program. You're all familiar with ADCs or antibody-drug conjugates, where a small molecule warhead is coupled to an antibody which targets that warhead and delivers it to cancer cells more selectively and allows a better therapeutic index. However, ADCs, as you know, are limited in targeting to the things that are on the outside of a cell. Most cancer targets are still on the inside of a cell. They're also more complex and expensive to manufacture. So a few years ago, we started a drug-drug conjugate program trying to make bispecific small molecules. So instead of the ADC, we substitute the A with another drug. And we found that by making these much smaller drugs, they can bind to both intracellular and extracellular targets or both. They're highly cell-permeable, and they're a lot simpler and cheaper to make. So the concept here is you take drug X against target X, drug Y against target Y. Both drug X and Y are FDA-approved agents. By fusing them in a way that we maintain both active sites, we can make a bispecific small molecule. But because these two FDA-approved drugs are fused and generate a new chemical entity, it's 20 years of new patent life. Our first DDC candidate is called NUV-1511. This is a derivative of a very widely known chemotherapy drug with a targeting agent that we have not yet disclosed. If you look at the xenograft experiments here, the black bar at the very top is untreated cancers. You can see they grow very rapidly. The light gray is the targeting agent alone. This is an FDA-approved agent that targets something to a target on cancer cells. It itself has no efficacy. If you look at the dark blue line, that's the maximum dose of the chemo warhead by itself. It has some efficacy, but because it's so toxic, it can't be given in a high enough dose sustainably to cause a significant effect. If we fuse the gray molecule to the dark blue molecule, we get the light blue line showing far more robust effects in these tumors and far more tolerability. We also can get some interesting properties with these DDCs that are almost antibody-like, but again, with small molecules. So in this experiment, in the dark blue line at the bottom, we've dosed 1511 for only two days. And yet, 28 days later, that tumor is still completely suppressed. So with these drug-drug conjugates, we can achieve pharmacology and PK that are unusual for small molecules. So this is in the clinic. We're targeting five indications, which are all large unmet needs and have very significant market potential. We're targeting women with breast cancer who failed Enhertu or Trodelvy. We're targeting women with HER2-negative metastatic breast cancer. Number three, men who failed Xtandi with castration-resistant prostate cancer. Four, women who failed platinum with ovarian cancer. And fifth, of course, very difficult to treat advanced pancreatic cancer. Our fourth program is a BD2-selective BET inhibitor. As you know, first-generation BET inhibitors have been very toxic and very ineffective. 868 is the most selective BD2-selective BET inhibitor in development. If you look at pelabresib's drug, which is a BD2-selective molecule, it's about five to six-fold selective for BD2, and 868 is about 1500-fold selective for BD2 over BD1, and there's evidence that by making a BET inhibitor more BD2-selective, you can improve its efficacy and tolerability. Here we're waiting to see what happens with MorphoSys and Novartis with their MF program with pelabresib. If that program does go forward and get approved, then this molecule will be quite interesting. We finished phase I before now. For now, we're waiting to see what happens to the MorphoSys compound. As I mentioned earlier, we have a very strong cash position with $549 million as of our last Q. Four programs in the clinic, two late stage, two early stage. We expect acceptance of our NDA later this year and a commercial launch in mid next year. And with that, I'm happy to take questions. Thank you very much. Okay, good. Just a couple of questions, David. That was fantastic. I guess first, obviously, congrats because you're on the verge of submitting and completing the NDA in the U.S. with breakthrough therapy. This is primarily a data set that evolved out of China. And I know that investors have been nervous a bit about the overall regulatory review package for that. Now, Peter Marks is here on Thursday. I'll invite you to check that out. But to what extent have you spoken with FDA about the filing and the package and to whatever degree you have to have a sufficient number of U.S. patients in that study? Just talk to that a little bit and the regulatory review we would expect. Right. So of the two pivotal studies, TRUST-I was an all-China study, but TRUST-II was a global study of which only 10% of those patients were Chinese patients. So the vast majority of those non-Chinese patients. We've had extensive discussions with the agency. The NDA submission did go in in October, and we feel very, very—I mean, we wouldn't make that statement if we weren't confident of acceptance of this NDA. So we believe the NDA will be accepted. We anticipate that by the end of the year, and we anticipate approval sometime mid next year. We think that this is a—we think one of the probably the most compelling facts is that the FDA has seen our data package and granted this program breakthrough designation in both first- and second-line. It's the only drug in development that's been granted first and second line designations. And the Chinese NMPA has also given us breakthrough designations. So we think that with a nearly 90% response rate and nearly four-year PFS, it's a hard data set to ignore. Right. So just to be clear, actually, that's a fresh reminder. Is that actually that the announcement of the acceptance of the NDA, probably with priority review, would be coming imminently in the next month or so? Generally, it's about two months after submission. So we submitted this at the end of October. Okay, end of October. And then to what extent can you give us confidence about how you would be able to compete this year with Bristol Myers? Bristol has. I couldn't tell you exactly what their sales were last quarter for that drug, but investors are a bit hesitant on the market. It needs to be developed. There needs to be more testing, but how are you going to compete with Bristol Myers? So repotrectinib sales have been poor. In the first two quarters, they generated about $14 million in revenues, and there was a slight uptick in the Q to about $11 million, but still relatively poor sales, but if you look at repotrectinib inhibitors, the CNS toxicity is quite severe. Patients have 65% dizziness. They have oftentimes problems with ataxia, loss of proprioception, difficulty walking, certainly driving, things that are lifestyle changing. I think that makes it very difficult for physicians to manage. Oncologists are very used to dealing with things like LFTs, which are a paper issue, not a clinical issue, and they have a lot of experience with it because so many oncology drugs elevate LFTs. Dizziness and CNS tox, not so much. That's a clinical problem that oncologists are not accustomed to dealing with. I think that's going to make it a very difficult adoption for oncologists. So I think that taletrectinib profile will be much easier for oncologists to use. And we anticipate a significantly better adoption among oncologists. Very good. Okay. And then the last question as we wrap up. Typically, small biotechs, as they get approved and launch a drug, typically finance. But I think you've got one of the healthiest balance sheets in all of biotech, actually. So tell us about your cash position. What do you need to raise? How is your position? So we were very fortunate to raise as much cash as we did. So we have about $549 million right now. We also, as I mentioned, are intending to partner Europe out. We have the possibility of out-licensing our 868 program, depending on what happens with.