All right. Welcome, everybody, to the J.P. Morgan Healthcare Conference. My name is Anupam Rama. I am one of the senior biotech analysts here at J.P. Morgan. I'm joined by my squad, Malcolm Kuno, Priyanka Grover, and Rashi Singh. Our next presenting company is Nuvalent, and presenting on behalf of the company is CEO Jim Porter. Great. Thanks, Anupam, for the introduction, and a sincere thanks to J.P. Morgan for the opportunity to present at the conference. It's a real pleasure to be out here in San Francisco with the greater biopharma community talking about bringing forward better options for patients, so I will be making some forward-looking statements in today's presentation. It's my honor to represent the Nuvalent team and tell you about the exciting company we're building. At the company, the mission is to create precisely targeted therapies for patients with cancer. The foundation of the company is a deep expertise in chemistry and structure-based drug design, so we're looking to bring innovative chemistry to make better options for patients with cancer. We focus on clinically proven kinase targets. The rationale there is simple. There are greater than 90 kinase inhibitors that are approved by the FDA. 70 of these kinase inhibitors are approved in oncology indications. So you can accelerate potentially the discovery and development phase because you're working on validated biology. You can run small, focused studies to understand if your drugs are working as intended. In order for us to make an impact in this space, we went to the physicians that have developed the earlier generation inhibitors. They are the experts. We understand from their perspective what are the limitations of the therapies that they help develop, what are the medical needs for the patients that they treat. And the two themes that emerge from those discussions are often around resistance and selectivity. Resistance is where the original therapies are no longer working because resistance mutations emerge and the patient's disease has progressed. Selectivity is a challenge because many of their first-generation inhibitors hit off-targets. Those off-targets can lead to adverse events, dose-limiting toxicities. If you make a more selective inhibitor, you could potentially hit the target harder, keep the patients on therapy longer, drive more durable responses. And that's how you get the best-in-class therapies that can move up the treatment paradigm and be an option for all patients with that given disease. So this all brings us forward to advancing our mission to build a sustainable company that can discover, develop, and ultimately deliver best-in-class medicines for patients with cancer, with the ultimate goal of maximizing the impact we can have for patients. So our portfolio is entirely internally discovered, and it's wholly owned. The three lead programs are all within lung cancer. So that includes zidesamtinib for ROS1 non-small cell lung cancer, includes NVL-655 for ALK-positive non-small cell lung cancer. Now, each of these two lead programs have demonstrated clinical proof of concept data. They both have FDA Breakthrough Therapy Designation. They're both expecting pivotal data readouts in 2025. Our third program is also within lung cancer. This is NVL-330 for HER2 non-small cell lung cancer. Beyond these three lead programs, we have a robust discovery portfolio, and the idea there is the same as the original programs. It's listening to the physicians, understanding where the needs are of the patients, and using innovative chemistry to bring forward options for those patients. Now, there are clear synergies in our portfolio. Each of the three advanced programs are all within lung cancer. You can imagine from a development standpoint, you're working with many of the same physicians, many of the same sites, so lots of learnings we can apply from one program to the other. The synergies also apply when you think about from a commercial standpoint. Launching three drugs into lung cancer indications is an obvious advantage as compared to launching a single product. Now, although each of these programs target different oncogenes, the premise of the programs is the same, and it's based on a simple premise of asking the question, "What if patients and their healthcare providers do not have to choose when making treatment decisions?" so there are a number of available therapies for a given clinically validated target. However, when making treatment decisions, physicians are often faced with understanding the trade-offs in making that treatment decision. Many of these original therapies suffer from one of the following setbacks. It could be inefficient coverage of resistance mutations, it could be limited brain penetrance, and these patients develop brain mets, or it could be the off-target inhibition leading to dose-limiting toxicities. Our approach is pretty simple. It's around the chemistry. Can we design a single molecule that addresses all these medical needs that are needed for patients? Let's look at that in the context of our two lead programs, starting on the left-hand side with ALK non-small cell lung cancer. There's actually six FDA-approved therapies for ALK non-small cell lung cancer, but you can think about it in this simple framework. When patients are newly diagnosed, they're often treated with the standard of care, which is alectinib. When patients progress on alectinib, they often progress with ALK mutations or CNS disease. The only drug that works in that setting is the drug lorlatinib. When patients progress on lorlatinib, they often progress with ALK mutations, either single mutations or compound mutations or CNS disease. Nothing works in that setting. And that's the immediate medical need the physicians asked us to try to focus on with our programs. Could we make an option for patients that have no available options in that third-line setting? Now, with our programs, we're looking not just to address the medical need, but how do we design an option for all patients with ALK non-small cell lung cancer? So looking at the earlier two therapies I mentioned, most physicians would tell you lorlatinib is the more active compound. It has some coverage of ALK mutations. It has good CNS penetrance. However, lorlatinib hits a specific off-target called TRK. The TRK kinase looks like the ALK kinase from a chemistry standpoint. So it's not a surprise that lorlatinib inhibits both ALK and TRK. Well, that's a problem for patients because if you inhibit TRK in the brain, it leads to a broad spectrum of neurotoxicities. For that reason, physicians have been reluctant to supplant alectinib with lorlatinib as their front-line option. That was a learning for us. If we can design a molecule that can do the things that lorlatinib can do, meaning cover solvent-front resistance mutations, have good brain penetrance, but importantly, is selective for ALK as compared to TRK, then we would have a better second-line option for ALK patients than lorlatinib, and we would have a better front-line option than alectinib for ALK non-small cell lung cancer patients. The challenges in ROS1 are quite similar. There are three approved therapies here. Crizotinib is the standard of care. Crizotinib is limited in that ROS1 resistance mutations will emerge, and it also has limited brain penetrance. Patients often progress with CNS disease. That represents a clear medical need where nothing really works well beyond crizotinib. If we could solve for a compound that hits the original driver, hits ROS1 resistance mutations, has brain penetrance, and is selective for ROS1 versus TRK, we can have a second-line option where clearly there's a medical need today. In addition, if we accomplish each of those things, we believe we'd have a better drug than crizotinib in frontline, drive more durable responses for all patients with ROS1 non-small cell lung cancer. Now, this strategy is not novel. This is a tried-and-true strategy in precision oncology drug development. One of the better-known examples is osimertinib in EGFR non-small cell lung cancer. Originally, this therapy was developed for patients that progressed on earlier-generation gefitinib or erlotinib, first-generation EGFR inhibitors. It solves for what the limitations for erlotinib and gefitinib were, meaning emergence of brain resistance mutations, CNS disease, and limiting the off-target inhibition of wild-type EGFR, which was dose-limiting in this context. It first gets the approval in previously treated patients, but eventually, it shows it can drive much more durable responses than the earlier generation inhibitors, nearly doubling the progression-free survival for patients, creating a better option for EGFR non-small cell lung cancer patients. This was also relevant from a commercial standpoint. It took what was a $2 billion peak sales opportunity for erlotinib and gefitinib and today represents a $5+ billion EGFR market. Now, that's interesting for Nuvalent because the ALK and ROS1 markets today are already interesting. We believe we have an opportunity with best-in-class therapies for ALK and ROS1 non-small cell lung cancer to drive much more durable responses for these patients. Within ALK today, alectinib is roughly a $2.5 billion market led by alectinib, which is just under $2 billion in sales. We're not looking to capture a portion of this market. We're looking to drive much more durable responses for these patients. If we could do that, we could potentially grow this very interesting market. Crizotinib is the market leader in the ROS1 space, delivering just under $400 million in sales in 2023. Again, we're not looking to capture this market. We're looking to grow this market by driving much more durable responses. In addition, beyond these front-line opportunities, the previously treated ALK and ROS1 markets are also interesting. Today, it represents about an $850 million market, and we note that these other therapies for these patients are limited. They were not designed to address these previously treated patient populations. Whereas our compounds, zidesamtinib and NVL-655, they were designed to address these patient populations. We have the potential to capture and grow this market in the near term. So that brings us to where we're going with these programs. The vision for the lead programs is we have the opportunity to disrupt the treatment paradigm with best-in-class therapies that address the combined medical needs in the ROS1 and ALK space. It also represents an interesting foundation to build a sustainable business. We have near-term registration strategies in place for previously treated ROS1 and ALK patient populations. We've already demonstrated compelling clinical proof of concept data in this setting. Both the programs have FDA Breakthrough Therapy Designation. The momentum we have speaks to the enthusiasm physicians have for these differentiated profiles. And we're going to expect pivotal data this year. We also have in place TKI- naive development strategies for both ROS1 and ALK, and we're moving forward on those initiatives. In doing so, we have the opportunity to bring forward options where physicians no longer have to ask the question on their treatment decision, "What if patients don't have to choose?" If you cover all those options, you can have an opportunity to address any line of therapy within ALK and ROS1 non-small cell lung cancer. So we'll move forward looking in the context of each one of these individual programs. We'll start with our ROS1 program. Zidesamtinib is our rationally designed ROS1 selective TRK sparing inhibitor. It's the first and only compound that's been designed to address the combined medical needs of hitting the original fusion driver, hitting ROS1 mutants, being brain penetrant to treat patients with brain mets, and importantly, selective for ROS1 versus that off-target TRK, which is dose-limiting. Now, the preclinical profile has been characterized extensively in the literature, and the clinical investigation is ongoing in the ARROS-1 study. ARROS-1 is a phase I to registration study, I'm sorry, study designed to support registration. The phase I enrollment is complete in this study, and we reported phase I updates at the ESMO meeting just last fall, where in these updates, we believe we demonstrated that each of the key areas of our target product profile were met. I'll walk you through that data. It starts with this is a very difficult-to-treat patient population. This is an advanced phase I patient population where patients have exhausted the available options, different than any other ROS1 study that we're aware of. As evidenced by there's three median lines of prior anti-cancer treatment, 66% of the patients received prior chemotherapy, 69% of the patients received at least two prior ROS1 TKIs, and 68% of these patients received TKIs other than crizotinib or entrectinib. These patient population also had the hallmarks of evidence of disease progression in the earlier lines. 38% of the patients had secondary ROS1 mutations, and over half the patients had a history of CNS disease. So the takeaway, a very difficult patient population to treat. And fortunately, zidesamtinib was active in this patient population because we designed it to be active in this patient population. Even in this difficult-to-treat patient population, a response rate of 44% by RECIST 1.1 criteria. The responses were durable. A median duration response was not reached. At the 12-month mark, DOR greater than 12 months of 67%. In these difficult-to-treat patient populations, the drug is active. The responses are durable. We also need to look at those key areas where the drivers of treatment progression. In order to move this earlier in the treatment paradigm, we need to demonstrate the drug is active in the key areas that patients progress on the other therapies. Looking at the ROS1 G2032R mutation, the most common mutation seen beyond crizotinib, we have patients that were repotrectinib- naive that have a 72% response rate. Even in patients that have been previously treated with repotrectinib, which was designed and intended to treat patients with ROS1 mutations, three of the eight patients respond. Looking at patients with CNS disease, this is an important component of our target product profile. We have an intracranial response rate of 50%. It's important to point out that seven of the eight of these patients had already been treated with a highly brain-penetrant ROS1 TKI. If they're progressing with CNS disease after a highly brain-penetrant ROS1 TKI and our drug is still active, it still clearly speaks to this drug has good CNS activity. Importantly, these CNS responses were durable. No CNS progression among any of the confirmed CNS responders. Finally, within our target product profile, safety may be the most important because remember, we're trying to design a drug that can move up in the earlier treatment paradigm. We want patients to take these therapies for a number of years to drive deep and durable responses. The drugs need to be well tolerated, and the safety profile that's emerged from zidesamtinib, it's very favorable. It's consistent with the ROS1 selective TRK sparing design. There were no treatment-related adverse events leading to discontinuation. No dose reductions due to TRAs was a low number at 8%. Now, although most of these patients in this phase 1 were heavily pretreated, where we're seeing these durable responses, there were a handful of patients that were less heavily pretreated that enrolled in the study, and interestingly, as we would expect, the data are very favorable as you push this drug earlier in the treatment setting, so patients that received just one prior ROS1 TKI, crizotinib, the standard of care, ± chemotherapy, eight of the 11 patients or 73% response rate was observed in this patient population, and not a single patient had progressed on therapy. It's really remarkable that this drug can do that in that setting. Now, we've really enjoyed tremendous collaboration from the treating physicians that we collaborate with globally on the ARROS-1 study. The enthusiasm they have for this differentiated profile really comes through when you look at the enrollment momentum we have in this program. Between the Phase I and Phase II ARROS-1 cohorts, we've enrolled 430 patients, and that includes just under 330 patients in the phase II since we opened it just this September ago. So incredible momentum here. It speaks to the excitement the physicians have for this differentiated profile. It speaks to the excellent collaboration we have with patient advocacy groups. It also speaks to the clear medical need, and it starts to paint a compelling clinical opportunity picture. And it really sets us up to deliver on these near-term milestones forthcoming in our ROS1 program. We have the ARROS-1 Phase II pivotal cohorts in previously treated patients that is going to be available from these cohorts in the first half of this year. We're also expecting to submit an NDA on these previously treated cohorts in the first half of, I'm sorry, in the middle of this year as well. While these previously treated cohorts are soon to be available, we're continuing to push forward and believe in the line-agnostic opportunity for zidesamtinib, and we're expecting to push forward on this TKI-naive cohort and work with the regulators to explore this line-agnostic indication as this data continues to mature. I'll pivot now to our second program, ALK. NVL-655 is our rationally designed ALK-selective TRK-sparing inhibitor. It's the first and only compound that's been designed to address the combined medical needs of hitting the original ALK fusion, being active against ALK resistance mutations, both single mutations and compound ALK mutations, have excellent CNS penetrance, and importantly, selective inhibition for ALK as compared to TRK to minimize those neurotoxicities seen with other drugs like lorlatinib, which have that brain penetrance TRK activity. Now, the preclinical profile has been described extensively in the literature, and the ALKOVE-1 study has been undergoing clinical investigation for the last couple of years here. ALKOVE-1 is a Phase 1/2 study. It's designed to support registration. The phase I enrollment is complete in this study. And just like with ARROS-1, we reported a data update from the phase I at ESMO just in the fall last year. Each of the key areas of our target product profile were demonstrated in that data update. I'll walk you through that quick update here. Just like ALKOVE-1, a very difficult-to-treat patient population. Patients have exhausted the available options as typical for a phase I study. This is evidenced by a median of three lines of prior anti-cancer treatment. Over half the patients received prior chemotherapy. 84% of the patients received prior lorlatinib where no other drugs work. 44% of the patients have received at least three prior ALK TKIs, including a second-generation and a third-generation like lorlatinib. There is also key evidence of the drivers of treatment progression on earlier therapies. Over half the patients have a secondary ALK mutation. About a quarter of the patients have these compound ALK mutations where no other therapies work. And about half the patients have a history of CNS disease. So clearly a difficult patient population to treat. And importantly, NVL-655 was active in this patient population because we designed it to be active in this patient population. With all available patients, we had a 38% response rate, and those responses were durable, median duration response of 14.4 months. And the patients that at the recommended phase II dose, where we believe we have better target coverage of the various ALK resistance mutation, a 38% response rate. And again, the responses are durable, median duration response not reached. And looking at the key drivers of treatment progression, starting with resistance mutations. On the left-hand panel, patients with single resistance mutations, the ORR was 55%. And again, the median duration response was not reached at the recommended phase II dose. In fact, only a single patient at the recommended phase II dose has progressed on NVL-655 as opposed at the time of this data cutoff. Also, when compound ALK resistance mutations, a 64% response rate, the median duration of response at the RP2D not reached. Looking at CNS activity, an important component of our target product profile, we're seeing intracranial responses in lorlatinib- naive patients. We're even seeing intracranial responses in patients that progress on lorlatinib. An excellent brain penetrance drug like lorlatinib, if you're progressing with CNS disease and you're responding to NVL-655, it clearly supports the drug is CNS active, and we're not seeing CNS progression among any of the confirmed CNS responders, and then maybe the most important component of our target product profile is the safety. Just to remind you, we want to be able to keep these patients on therapy for extended periods of time. The drug needs to be well tolerated. NVL-655 is behaving like we designed it. As As an ALK selective TRK sparing inhibitor, we're not seeing those neurotoxicities associated with TRK inhibition. We have a low discontinuation rate due to treatment-related adverse events and a 15% dose reduction rate due to treatment-related adverse events. Although most of the patients in the phase I were very heavily pretreated, we also were lucky to see some physicians enroll some less heavily pretreated patients in this study as well. These would be those second-line patients that have yet to receive lorlatinib. In this setting, it's clearly showing that NVL-655 is active in this setting. A 57% response rate to recommended phase II dose, and only a single patient had progressed in that lorlatinib naive setting. Looking at patients with lorlatinib naive with resistance mutations, not a single patient had progressed in that setting. So it clearly portends well as we think about moving this up earlier in the treatment paradigm. The enrollment on the study has been remarkable. It has exceeded our expectations. Again, thanks to the tremendous collaboration we have with physicians and the patient advocacy groups that clearly recognize this differentiated profile. We've enrolled nearly 600 patients between the phase I and phase II components of the ALKOVE-1 study. 463 patients since the study just opened 10 months ago. 463 patients in 10 months. It speaks to the medical need. It speaks to the interest from the physicians and the patient advocacy groups. It starts to paint that compelling commercial opportunity with NVL-655. It sets us up well for these milestones that are forthcoming from our ALK franchise. Within ALKOVE-1, we're expecting the previously treated both second-line and third-line data to be available in 2025. We also are initiating our frontline development strategy, ALKAZAR study, designed to support registration in TKI-naïve ALK patients. This is going to compare NVL-655 to the standard of care alectinib in a one-to-one fashion with progression-free survival as their primary endpoint. We expect to initiate that in the first half of this year. I'll move now to our third program, NVL-330. This is targeting HER2 lung cancer. Now, the needs in HER2 lung cancer are really driven by coverage of HER2 exon 20, which is the major driver within HER2 lung cancer, and having a wide index for inhibiting HER2 exon 20 compared to wild-type EGFR. That is the dose-limiting toxicity, leads to skin toxicities, GI toxicities. NVL-330 solves for that. In addition, because these patients have lung cancer, you need excellent brain penetration. And NVL-330 also solves for that. The preclinical profile has been described in the literature for this compound, and it sets us up to execute on our HEROEX study. This is a Phase 1a/1b dose escalation study. We started it in July of this year. Standard study design to understand the safety, tolerability, identify the recommended phase II dose for NVL-330 to take forward in other HER2 lung cancer opportunities. I'll close with this. Last year, we rolled out our OnTarget 2026 strategy, which is our opportunity to bring our first potential product to patients in 2026. We made tremendous progress in this initiative with hitting all of our milestones in 2024. And it sets up 2025 as an outstanding year where pivotal data is going to be available for our previously treated ROS1 and ALK studies. We're also going to initiate our ALKAZAR frontline ALK strategy. We're going to further advance our HER2 program. And it gets us all closer to our mission of ultimately building a company that can discover, develop, and deliver best-in-class medicines for patients with cancer. I'll close with this. It's an honor to work, and I have to acknowledge and recognize the Nuvalent teams. It's an honor to work with them. Their passion for bringing forward new options for patients with cancer is really inspiring, and I'm fortunate to collaborate with them in doing so. Thanks for your attention. I'm happy to take your questions. Thanks, James. I just want to remind folks that there are three ways to ask a question. If you want to raise your hand, I can call on you. You can submit questions through the portal, or you could just email me as well. James, you talked about for the ALK program, you'll have pivotal data. It sounds like you'll have pivotal data from two cohorts, right? Second and third line. Maybe just remind us of the benchmarks on response rate that we should be considering in ALK. Sure, sure. There's been tremendous progress on the ALKOVE-1 study. Their enrollment really speaks to why the physicians and patients are so interested in this program. We are going to have data availability for both the second-line and third-line cohort. Just to remind you, alectinib is a standard of care. When they progress on alectinib, lorlatinib is that option. When they progress on lorlatinib, nothing works. So in that third-line setting, there is no benchmark. No other therapy works. So if the drug is active and the responses are durable and the drug is well tolerated, you can envision that there's a pretty straightforward development strategy. In fact, that's where we have FDA Breakthrough Therapy Designation. I think it also speaks to how they view it as a clear medical need. In the second-line setting, lorlatinib is a standard of care. Lorlatinib has roughly a 31%-39% response rate with a seven-month duration response. We do not think that's good enough for patients. Driving seven months durability is not good enough after patients progress on alectinib. And there's a reason for that. Lorlatinib has a narrow index for inhibiting ALK resistance mutations compared to off-target TRK inhibition. That was the dose-limiting tox in its development. We knew that from the outset. We had worked with the physicians that have developed these earlier generation inhibitors. They told us to try to use innovative chemistry to make a better molecule that can address that need. NVL-655 has that profile. It has that wide index for hitting ALK mutations compared to lorlatinib and avoiding those off-target TRK dose-limiting toxicities. We're seeing that in our phase I data. We see durable responses even in patients that progress on lorlatinib. And those lorlatinib-naive patients, we've only seen a single patient progress on NVL-655. And it really speaks to why ALK is such an interesting driver. The tumors are entirely dependent on ALK signaling. And if you can broadly cover ALK and the ALK mutations, you could potentially drive very durable responses in this setting. Just in terms of the scope of the data that we would be getting, in the second line, will you have enough follow-up and durability to show differentiation relative to the seven months that you just talked about? Yeah, I mean, it's always going to be dependent on the data, so until we see the data, it's difficult to answer the question, Anupam, but based on what we've learned from the phase I, we're quite encouraged with the response rates and the durability we're seeing in that setting, and it puts us on a track, we believe, to have data availability this year in our ALK program to look across that second-line and third-line setting. Questions from the audience? Then maybe a similar question, right, for ARROS-1, where you'll also have data second and third line. Maybe walk us through the benchmarks and considerations there on the efficacy side. Yeah, so in the ROS1 space, no drug has ever been designed for ROS1 patients until zidesamtinib. We heard that loud and clear from the physicians. All the drugs that are available for patients are repurposed drugs that target other kinases. They also happen to target ROS1, but it leads to challenges in the treatment decision-making because the physicians are making those trade-offs of, do I bring in toxicity or do I bring in limited brain penetrance to try to get patients to respond to these types of therapy? We want to solve for that through innovative chemistry. So in frontline, patients receive crizotinib. It has limited brain penetrance, and it has emergence of ROS1 resistance mutations. Zidesamtinib solves for both of those things. So the benchmark there is a duration response of 18 months. That's what crizotinib can deliver. In the previously treated setting, there really are no good options. All the other therapies we've tried to develop here are mostly dual TRK ROS1 inhibitors. They have significant neurotoxicity signals. The physicians have been more reluctant to use those therapies to replace crizotinib in the ROS1 setting. So we should point out that crizotinib used to be the standard of care in ALK non-small cell lung cancer. But much better therapies were developed in that setting, and crizotinib is no longer used. So the limitations crizotinib had in ALK non-small cell lung cancer are the same limitations it has in ROS1, the emergence of ROS1 mutations and CNS disease. So if the other therapies could do that in the ALK setting, it speaks to why zidesamtinib could also do it in the ROS1 setting. We have an email question here, which is, how long would it take to show that your ALK inhibitor is not worse than lorlatinib in the frontline versus, say, a study against alectinib, which may take many years, five, six years? Yeah, so I think we're really aided in this setting that there's 15 years of clinical research available in the ALK setting. We're not breaking new boundaries here. The innovation here is really the chemistry, right? The biology of ALK disease is well known, and there's multiple, there's now six approved ALK therapies that we have the benefit from learning from, right? So it really was, could we make a molecule that solves for those limitations that we learned about through the clinical investigation of those other drugs? And we did so with NVL-655. So their choice to run a randomized trial versus alectinib was really straightforward. We talked to investigators globally. This is the standard of care. They also recognize that it's a limited drug and that these patients can progress with CNS disease or with ALK resistance mutations. I should point out, in the ALK setting, many of these patients are diagnosed when they're younger. They're often in their 30s, their 40s, and 50s. Alectinib has been a great option for these patients. It delivers a couple of years of progression-free survival, which is a phenomenal outcome for patients that have lung cancer. However, if you're in your 30s, 40s, or 50s, a couple of years is clearly not good enough. These patients deserve better options. We think NVL-655 could be that better option, drive much more durable responses, and we're really excited to run this experiment. Questions from the audience? Jim, what do you think are the most misunderstood points by the street when it comes to the refractory commercial opportunity in ROS1 and ALK? Yeah, since there are no real good ROS1 refractory options, it's difficult to paint that picture of what that market is. But if you start to look at the durability that we've generated, even these heavily pretreated patients, you can envision, one, making an impact for patients, but two, potentially building a compelling commercial opportunity because you can keep patients on therapy for a long period of time and drive durable responses. I think in the ALK setting, one of the things that's very interesting is today, lorlatinib is a $500 million market in the ALK non-small cell lung cancer space. Lorlatinib, as I mentioned, is not the optimized drug in that previously treated ALK setting. In fact, none of the other ALK drugs are really optimized, whereas NVL-655 has been optimized for that setting. So if we can drive much more durable responses in seven months in that setting, which our phase I data clearly points to that we're trending in that direction, then you could potentially start to capture and grow that previously treated market. And that's a near-term opportunity that's right in front of us at Nuvalent. Questions from the audience? Maybe a quick one from me. You'll be filing soon, but what would be the sales infrastructure that would be needed to address the refractory market in both settings? Yeah, so firmly believe at Nuvalent, our team has the mission to build a sustainable company. I believe the sustainable companies need to do three things really well. You need to be able to discover drugs, you need to be able to develop them, and you need to be able to ultimately deliver them. I think we've done an outstanding job at building the discovery and development organization. The proof is in the data we just walked you through. The opportunity is right in front of us now to build that commercial capability. We started that in early 2024. We made tremendous progress. We're well on our way for being prepared to launch our drugs in 2026. We hired the head of commercial in early 2024. I'm not ready to get into the specific details of what that commercial organization will look like today, Anupam. However, I will tell you that we're benefited by not breaking new ground here. These are established markets. Again, drugs have been approved in the ALK and ROS1 space for over a decade now, so we can learn from those other therapies that have been developed, those other markets that have been established, and we can guide our commercial design registration strategies accordingly. Last call, any questions from the audience? All right, thank you, Jim.