Nuvalent, Inc. (NUVL) Earnings Call Transcript & Summary

Welcome, everybody, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Rati Pinhe, Joyce Zhao and Priyanka Grover. Our next presenting company is Nuvalent and presenting on behalf of the company, we have CEO, Jim Porter. Jim?

Thanks, Anupam. Thanks to the JPMorgan team for the opportunity to participate in this year's healthcare conference. It's always a pleasure to be out in San Francisco with a greater biopharma community talking about making new medicines for patients. So I will be making some forward-looking statements in today's presentation. It's my honor and privilege to represent the Nuvalent team and tell you about the exciting company we're building. Our mission is to create precisely targeted therapies for patients with cancer. It's anchored on a deep expertise in chemistry and structure-based drug design. That's a special sauce of the company. I'm a chemist by training. Our team prides itself on bringing innovative chemistry solutions to patients. We focus on validated biology, so clinically proven kinase targets. There are over 100 approved kinase inhibitors today by the FDA. 85 of these kinase inhibitors are approved for patients with cancer. So working on validated biology, you can accelerate both the discovery phase, working with validated targets. So you can accelerate the development phase by running small focused studies to understand if your drugs are working as intended. And for us to make an impact in this space at the outside of the company, we say, let's go form relationships with the physicians that have developed the earlier generation kinase inhibitors. Let's learn from their perspective. What are the limitations of the therapies that they use for their patients or the needs of the patients that they treat? And the 2 themes that emerged from those discussions are around kinase resistance that is the original kinase inhibitor stop working because resistance mutations have emerged. Let's design innovative chemistry solutions for those challenges and kinase selectivity, often kinase inhibitors, they hit additional off-target that don't relate to the disease and hitting those off targets could lead to dose-limiting toxicities. If you have a more selective inhibitor, not only can you hit the target harder, you can keep the patients on therapy, and that's the best way to predict more durable outcomes for patients by driving more durable outcomes. That's how you get to best-in-class therapies that can move up the treatment paradigm and maximize the impact for patients. So it's with those simple concepts that we launched the company about 7.5 years ago, and we've advanced the portfolio of potentially best-in-class products with complementary initial indications in non-small cell lung cancer. So at the forefront of our portfolio, we call them parallel lead programs. It's zidesamtinib, targeting ROS1 non-small cell lung cancer and neladalkib targeting ALK-positive non-small cell lung cancer. Now both of these programs have generated pivotal data. Both of these compounds have FDA breakthrough therapy designation. We made a lot of progress advancing each of these programs. The zidesamtinib for ROS1 non-small cell lung cancer. We submitted an NDA and the NDA has been accepted by the FDA with an expected PDUFA date of September of this year. In addition, we have a TKI-naive registration cohort that we're continuing to make progress for those ROS1 patients as well. And for our ALK program, we also submitted an NDA -- I'm sorry, We've presented pivotal data late last year, and we have an NDA that we're going to submit in the first half of this year. Late last year, we aligned with the FDA on our submission strategy for neladalkib for previously treated ALK patients. In addition, we have an ongoing randomized Phase III comparing our drug neladalkib to the standard of care alectinib in TKI-naive ALK-positive non-small cell lung cancer patients. It's our drug neladalkib versus alectinib, randomized 1:1 450 patients, progression-free survival as the endpoint. Now further down the portfolio, we're very excited about our third program. This is targeting HER2 lung cancer and the compound is NVL-330. There's a clear opportunity to address the need in HER2 lung cancer with the HER2 TKI, there's other places we can take such a drug that has this profile. Selectivity for HER2 versus off-target wild-type EGFR inhibition as well as excellent brain penetrant. So a really interesting molecule early in our pipeline. Now with those 3 programs targeting in non-small cell lung cancer, there's obviously some synergies working with many of the same sites, many of the same physicians with 3 different lung cancer programs. There's obvious synergies that we can take advantage of in our portfolio. Also, when you think about building a commercial organization, having 3 products to launch as opposed to a single product has also created some excellent synergies. So as a whole, we look like a lung cancer company. That's actually not the case. We are a chemistry-based company. We have a number of discovery programs we're working on beyond these 3 linked programs and the idea is the same. We listen to the physicians. We understand where the needs are, and we find out where can we apply innovative chemistry to come up with better solutions for patients with cancer. So for today's discussion, I'm going to focus on our parallel lead programs targeting ROS1-positive non-small cell lung cancer and ALK-positive non-small cell lung cancer. So with all the progress we made last year, we have an excellent position to unlock the potential for making an impact for patients with these diseases. The pivotal data we generated from both programs shows the potential to deliver meaningful durability and tolerability for patients with these cancers. We have a growing team, about 240 team members representing the Nuvalent team or we're building those -- that infrastructure to launch these drugs in the U.S. this year. We're also well capitalized. We have a runway into 2029 that allows us to push forward on these programs. So the theme for this today's discussion is we see a vision where for ROS1 non-small cell lung cancer reimagining what is possible for patients that have this disease. And within ALK-positive non-small cell lung cancer, realizing the full potential of a potentially best-in-class ALK TKI. So I'll start with ROS1 non-small cell lung cancer. And pictured here is Jim. Jim's a patient living with ROS1-positive non-small cell lung cancer. Someone who's advocates fiercely for ROS1 non-small cell lung cancer patients and an excellent collaborator for Nuvalent, really privileged to get to know Jim as he's advocated for patients with his disease. What Jim has in common with many patients diagnosed with the disease, they're often younger. They're often in the 30s, 40s or 50s. They have a lot of personal and professional milestones ahead of them. And they don't want the cancer to dictate or the treatment to dictate their day-to-day. Jim lives an active life, just like many patients. And we share that vision with Jim as someone as creating -- reimagining what's possible for these ROS1 non-small cell lung cancer patients. So in the treatment paradigm, there's actually approved therapies already for patients with ROS1 non-small cell lung center. The standard of care has been crizotinib. It's a drug that works quite well. Patients can stay on therapy. It drives durable responses, although it has some limitations. Patients can progress with on crizotinib with ROS1 resistance mutations or it's not highly brain penetrant so they can progress with CNS disease. So there are 2 limitations that we wanted to solve for with zidesamtinib. There are other drugs that have been developed and approved that tried to solve for one of those or both of those limitations. But what they often have in common is they hit off targets that are dose-limiting. And hitting those off-targets that are dose-limiting like the structurally related kinase track, at least to a broad spectrum of neurotoxicities and physicians have been reluctant to replace crizotinib with those other agents. It also impacts the durability, the amount of time you can keep those patients on therapy that hit those off targets. So we want to solve for that medical need as well. And when patients in that third line, there's currently no option available for those patients. So we see clear potential opportunity for patient impact across all 3 lines of treatment. And third line where nothing works. And second line, we think we can drive much more durable responses by hitting the mutations harder, keeping patients on therapy and in frontline, by addressing those key drivers of disease progression, CNS disease and ROS1 mutations, we think we have a clear opportunity to drive more durable responses. So in reimagining what's possible, understanding the background with crizotinib, it drives relatively interesting durable responses, 19.3 months median progression-free survival in frontline patients. But what's known in the target oncology space that there's drugs that have done better across other indications. And one example is lorlatinib in ALK-positive non-small lung cancer, driving over 5 years of progression-free survival, significantly longer than what crizotinib can do in the ROS1 space. And the way the lorlatinib does that, it hits those key drivers of treatment progression, ROS mutations or CNS disease. So we think that we can do that within ROS1 non-small cell lung cancer, we can transform the expectations for patients that have this disease, potentially driving meaningfully more durable responses and having better tolerability. This also is an interesting aspect for building an organization around because it represents a clear market opportunity. There's already an interesting market in ROS1 non-small cell lung cancer. And by driving more durable responses, you're talking about more time on therapy. More time on therapy leads to a broader market opportunity because you're going to build up that prevalent patient population. So our solution for ROS1 non-small cell lung cancer patients is zidesamtinib. This is the first and only drug that's been designed to address the combined medical needs of hitting the ROS1 fusion that drives the original disease. Having excellent coverage of ROS1 mutations that have emerged beyond earlier generation inhibitors, having excellent CNS penetrants to either treat patients with CNS disease or to prevent disease from spreading to the brain and importantly, being selective for ROS1 versus off targets like Trk. Trk inhibition being that dose-limiting toxicity. So with zidesamtinib at hand, we worked with our collaborating physicians to design the ARROS-1 study. This was a Phase I/II study designed to support registration in ROS1 non-small cell lung cancer patients. Phase I, typical objectives, understand the safety, identify a dose, Phase II, registration-directed cohorts in both previously treated ROS1 non-small cell lung cancer patients as well as TKI-naive patients. A few things that stick out with the execution of the study. First is the enrollment. The enrollment has been massive on the study, 540 patients between the Phase I and Phase II study, significantly over enrolling what the original projections for the study were based on the enthusiasm for this differentiated profile from the investigators, from the patient advocacy groups, represents the clear medical need and it starts to paint a compelling picture what the commercial opportunity might be for -- in the ROS1 non-small cell lung cancer space. The other thing that sticks out about the execution of the study is just how difficult the patient population was to treat. This was an advanced heavily predated patient population that have progressed through the other therapies. It's different than any other ROS1 study that we're aware of as evidenced, despite how highly treated these patients were before, about half the patients with CNS disease. About 1/3 of the patients with ROS1 resistance mutations. About half the patients have received at least 2 prior ROS1 TKIs, including brain penetrant drugs like lorlatinib, repotrectinib, taletrectinib. This population has never been studied by any other ROS1 drug because it's a difficult patient population to treat. But even in this very difficult patient population to treat, our drug was active, and it was active because we designed our drug to be active for any ROS1 patient. So starting in that most heavily pretreated patient population on the bottom of the slide, patients that have exhausted available options our drug is still active, a 44% response rate by RECIST 1.1 criteria. It's active in the key call marks of disease progression. ROS1 resistance mutations like the ROS1 G2032R mutation, 54% response rate. It's active in the CNS, an intracranial response rate of 48%, including patients that have complete responses. We see the safety profile that's indicative of a ROS1 selective Trk-sparing compound. We are not seeing those off-target neurotoxicities that have been seen with those other ROS1 agents in this space and patients are staying on therapy. We're seeing very low discontinuation rates or dose reduction rates due to treatment-emergent adverse events. And what that's resulting in is patients having durable responses. They're staying on therapy, they're having durable responses. 62% of the patients are still in response at that 1.5 years landmark. Now for patients that are less heavily pretreated, they've only received 1 prior ROS1 TKI like crizotinib or entrectinib, Again, the drug is active. Drug is active. What really stands out here is the intracranial activity. 85% of the patients have a response in the intracranial compartment, including over half of these patients that had an intracranial complete remission. That has not been seen to any other ROS1 TKI, truly differentiating this as a highly brain penetrant drug and addressing really what the design goals were for the program to make a highly brain penetrant drug that can broadly cover ROS1 resist mutations. And that results in the durability we're seeing 93% of the patients still in response at that 1.5 years landmark. And that simply does not happen in oncology drug development. What we are seeing is better durability the later lines of treatment. So patients have already taken crizotinib and their durability looks better than crizotinib after they've already received crizotinib. In oncology, drug development typically responses durations go down in subsequent lines of treatment, and we're seeing it go the other direction. And it really speaks to the attributes of zidesamtinib and the design goals for the program. Now we also have an ongoing TKI-naive registration cohort. We showed a preliminary snapshot of the early data from this cohort, including 35 patients. Here we see the response go even higher 89%. We see the high intracranial CR rates and that's translating to the durability. 96% of the patients still in response at that year landmark. So our goal is to drive durable responses for all patients to drive better outcomes for patients that have this disease. But we're also building the business, right? And this is an interesting commercial opportunity. Just by doing some simple math, you can take -- you can easily see what looks like an interesting market today. You drive more durable responses, that means more time that patients are receiving therapy, more time on therapy means expanding the market. And we can clearly see just by some simple calculations here, how the today's ROS1 market could grow to something more like $1.5 billion to $2 billion, closer to what the ALK market is today as opposed to the ROS1 market. That represents a clear interesting opportunity for Nuvalent. So I'll now pivot to ALK-positive non-small cell lung cancer. It's a related program. Many of the same challenges that we're trying to solve for with our ALK program. And here I'm introducing Kirk. Kirk is a patient living with ALK-positive non-small cell lung cancer. He's also the President of the Board of an ALK positive patient advocacy group, someone that we collaborate quite closely. And over the years, I've been privileged and honored to call Kirk a friend. Kirk aspires to a day where patients with ALK-positive non-small cell lung cancer could be managed as more of a chronic condition as opposed to a life-threatening disease. And we share that aspiration to have that those types of outcomes for patients without positive non-small cell lung cancer. So the treatment paradigm, again, there's approved agents in this space, starting with alectinib, which is the standard of care. Most patients in frontline will receive this agent. It works reasonably well. It drives durable outcomes for patients. However, it has some limitations, patients will progress with ALK resistance mutations or with CNS disease. And the only drug that works beyond alectinib is the drug lorlatinib. And the reason it works, it has some coverage of ALK resistance mutations, and it has excellent CNS penetrants. Now when PACE progress on lorlatinib, nothing works in that setting. The reason they're progressing, they either have inefficient coverage of ALK single resistance mutations or a development of a second mutation what's called the compound mutation where lorlatinib is not active. We said, okay, that's a clear medical need. Let's try to solve for that with our program and third line to address the need where patients have no options, right? We see additional opportunities for patient impact as well across all lines of treatment. We want to solve for a third line where nothing works, but we want to be the drug for any ALK non-small cell lung cancer patients. So we look at the earlier lines, most physicians would tell you that lorlatinib is the more active drug. It's a more active drug than alectinib. However, it doesn't get a lot of frontline uptake because it hits a specific off-target called Trk, at least to a broad spectrum of neurotoxicities. So if we could engineer that at the molecule, we could potentially drive much more durable outcomes in that second-line space as well as a much better outcomes for frontline patients with alectinib. And it's known that drugs can do this type of thing. So alectinib as I mentioned, the standard of care, it's already known that a drug like lorlatinib, which addresses some of those drivers of disease progression can more than double the durability seen for patients without positive non-small cell lung cancer. However, as I mentioned, there are challenges with lorlatinib, we hit specific off targets that are dose limiting. So many physicians have been reluctant to replace alectinib with lorlatinib. And if we can address those liabilities, we can have the potential to deliver transformative durability and tolerability for patients without positive non-small cell lung cancer. This also represents an interesting commercial opportunity as the market today is interesting, and we know that there's a very motivated patient population that wants better outcomes for patients with ALK-positive non-small cell lung cancer as evidenced by the execution in our studies. And if we think if we could work with those patient groups, we could potentially realize the full potential for patients living with ALK positive non-small cell lung cancer by growing that prevalent patient population where it's seen more as a chronic condition as opposed to a life threatening disease. So our solution for ALK-positive non-small cell lung cancer is neladalkib. This is the first and only drug that's been designed to address the combined medical needs of hitting the original ALK fusion that's driving the disease, having activity against ALK single mutants, having activity against ALK compound mutants having excellent CNS pensions to either treat patients with CNS disease or prevent disease from spreading to the brain and importantly, is selective for ALK versus off target Trk inhibition, which is dose limiting. With the drug in hand, we worked with our collaborating physicians to design the ALKOVE-1 study, very similar to what I discussed for ARROS-1. It was a Phase I/II registration study. In Phase I, understand safety and the dose. Phase II, we had registration-directed cohorts in previously treated ALK non-small cell lung cancer patients. The enrollment on this study has been off the charts, 781 patients. The original protocol called for about 250 patients. We exceeded that by 3x. That was for a reason. Incredible patient demand for this differentiated profile. Clearly outlining the medical needs for this patient population, the investigator and patient enthusiasm to a differentiated profile and representing a compelling commercial opportunity for our program. With that excellent execution that allowed us to quickly progress to having pivotal data, which we presented late last year. Another interesting anecdote from this pivotal data is just how heavily pretreated these patients were. As evidenced by 3 median lines of prior anticancer treatment, over half the patients have received prior chemotherapy. About 19% of the patients had the secondary ALK GR mutation, one of the most common mutations seen beyond alectinib and 40% of these patients with CNS disease. This is a difficult patient population to treat. Now about 1/4 of these patients were a little bit less heavily pretreated. They've yet to receive lorlatinib as a second-line agent. About 25% of the patients that had were lorlatinib-naive. Now 25% of these patients received prior chemotherapy. 100% of these patients have all received a second-gen ALK TKI of whom 70% received alectinib. The other 30% are either receiving alectinib plus crizotinib or alectinib and brigatinib or some combination thereof. And about 1/3 of these patients with CNS disease. So a difficult patient population to treat, but not surprisingly, our drug is active in this difficult patient population to treat because we designed it to be active in these difficult-to-treat patients. Starting at the bottom for patients that have already received lorlatinib or nothing else works. 26% of these patients respond and the responses are durable. We're seeing a median duration of response of 17.6 months. Now that is double the durability of lorlatinib beyond lorlatinib. Again, that simply does not happen in oncology drug development. Typically, the durations of response get lower and lower in subsequent lines of treatment. And we are doubling the durability behind the line of therapy above it, really interesting results for the Nuvalent team. In the broadest patient population, where patients have received any prior ROS1 ALK TKI with a 31% response rate, we're seeing those key hallmarks of our target product profile, activity against the mutations where the response rates go up even higher. We're seeing activity in the intracranial compartment, including intracranial complete remissions. We are seeing a safety profile that's indicative of the ALK selective Trk-sparing design. We are not seeing those off-target neurotox signals that other drugs like lorlatinib see. And we see low discontinuation rates and reduction rates due to treatment-emergent adverse events. And that's translating to the durability. We're keeping patients on therapy. We're hitting the drivers of disease progression. 53% of the patients are still in response at that 1.5 years landmark. If you go to the patients that are less heavily pretreated, the lorlatinib-naive patients, the response rate goes up even higher, 46%. We start to see higher CR rates in the brain, translating to 60% of the patients still in response at that 1.5 years landmark. Very encouraging durability we're seeing across all lines of treatment. That's 60% duration of response at that 1.5 years, we're seeing alectinib like durability beyond patients receiving alectinib. Again, that typically does not happen in oncology drug development, very encouraging. Now we have an ongoing Phase III in naive patients, but we had an exploratory cohort within the context of the Phase II. We shared an update from that preliminary cohort where we've seen the 44 patients, the response rates go even higher, 86%. We see the high CR rates in the brain, and that's translating to durability, 91% of the patients still in response at that year landmark. So we're very encouraged by the overall durability and tolerability we're seeing from our data and it starts to paint an interesting opportunity to maximize the outcomes for patients without positive non-small cell lung cancer. And just like with ROS1, it represents an interesting commercial opportunity. The ALK market today is already interesting. Alectinib drives about a couple of years of progression-free survival and has built up a $2-plus billion market in this space. We'll just envision patients having more durable responses, more time on therapy, and you can quickly get to calculations where you can considerably grow that out market to look something more like what today's EGFR market looks like. That's a very attractive opportunity for Nuvalent to focus on. All the progress we made thus far brings us to a very exciting 2026 where we had a number of exciting milestones ahead of us. These milestones include potentially the first approval for our portfolio in zidesamtinib for previously treated ROS1 non-small cell lung cancer patients. We have a PDUFA date of September of this year, and it's under FDA review. In addition, in our ROS1 program, we expect our TKI-naive data from our ROS1 patients to be available, and we will submit that data to the FDA in the second half for potential line agnostic indication down the line for ROS1 non-small lung cancer. For our ALK program, late last year, we aligned with the FDA on a submission strategy for neladalkib for previously treated ALK non-small cell lung cancer patients. We will submit that NDA in the first half of this year, and we will continue to progress our ongoing Phase III ALKAZAR study for patients with TKI naive ALK positive non-small cell lung cancer. We're really excited about our HER2 program, and we continue to progress that Phase I heroics program, NVL-330 and HER2 lung cancer. And we continue to invest in the discovery portfolio. We expect the next development candidate to emerge from our discovery portfolio in 2026 to bring our fourth program for patients. So we always believed that we aspire to build a sustainable company. And it's our belief that sustainable companies in our industry need to do all 3 phases well. They need to be able to discover new drugs. They need to be able to develop new drugs and they ultimately, they need to deliver those drugs to patients. We think we made incredible progress on the first 2 phases. Our discovery engine has been improving. Just 7.5 years stringing this company from scratch. We've taken 2 programs from scratch, discover them, develop them, now submitted 1 NDA about to submit another one. Our development team, the execution has been phenomenal, pushing these programs forward at an incredible pace our ROS1 program alone enrolled 700 patients between our ARROS-1 study and our ongoing expanded access program. Our ALK program enrolled over 1,000 patients between our ALKOVE-1 study and our expanded access program. I mentioned before, we believe our ALK program is one of, if not the fastest, enrolling small molecule oncology trial in the history of our industry which really speaks to the opportunity we have in front of us with neladalkib. This puts us in a position to build that third leg of the stool to build our capabilities to deliver the drug to patients. We are well on our way of building our U.S. commercial infrastructure to put us in a position to realize that mission of building a sustainable company that can discover, develop and deliver best-in-class solutions for patients with cancer. So what does it look like beyond this year? We have incredible opportunities in front of us. We expect that we'll be able to potentially launch neladalkib for ALK-positive non-small cell lung cancer patients, expand the indications for both ROS1 and ALK to TKI-naive patients. We have the opportunity to build a sustainable U.S. business as a commercial leader in this space. We've enjoyed excellent resources and support, bringing into the company that puts us in a position to potentially build a sustainable company. And we recognize how unique that is in our industry. Very few companies ever get to the point where they can think about one, launching products; and two, how to build a sustainable organization. We recognize we have that opportunity in front of us. and we're incredibly excited about it. This also puts us in a position of, let's not settle just for the U.S. market. There are plenty of patients around the world that need neladalkib and zidesamtinib. Let's deliver that -- those drugs to patients. We're starting to build the capabilities now of how can we commercialize, not just in the U.S., but in those other geographies where patient needs exist. And further down our portfolio, we have a number of exciting programs we have we're working on that potentially provide that fuel to continue to build the organization. So investing in those programs for indications within the lung cancer and also beyond lung cancer represents an incredible opportunity for us to fulfill our mission of bringing new potential best-in-class medicines for patients with cancer. So I'll just close with thanking all the collaborators, the consultants, the patients, the investigators that have helped us with the execution of building this company, the Nuvalent team for their passion for developing new options for patients with cancer. It's truly a privilege to collaborate with them in building this company. Happy to take your questions.

Thanks, Jim. I'll ask the first couple of questions, and then I'll open it up to the audience to get into questions as well if you choose. But I wanted to touch a little bit on the TKI-naive ROS1 non-small cell lung cancer. It looks like you're going to be filing in the second half for expansion. Will we get some of that data ahead of time to understand what you're filing and what that profile looks like in the front line?

Yes. Yes. Thanks, Anupam. So we presented a snapshot of the first 35 patients, which you mentioned looked encouraging. Yes, that data will mature this year. We will submit it with the FDA. We haven't guided to exactly when we'll share that data, but you can imagine that we know folks will be interested to see how that matured. And I'm sure we'll have an update in the future of when you expect to see that.

And then also, what are the gating factors then for the ALKOVE-1 refractory setting and getting that filing submitted. You guys got a standard review for ROS1. So should we be expecting a standard review here as well?

Yes. So this ALK program, we started in our clinical development in the middle of 2022. And we're talking about submitting an NDA in the first half of 2026. Just remarkable execution from start to finish for our program, treating over 1,000 patients with neladalkib, just an unbelievable program. Those 1,000 patients creates a lot of work. There's a lot of data to clean, a lot of data to generate and put it all together in NDA package. Now our team has executed phenomenally on this. We've been planning for seamless transitions between preclinical to Phase I to Phase II and now approval. So we're well on our way of completing that NDA submission. Many of the modules have been written prior to having the data. Late last year, we aligned with the FDA on the NDA submission strategy, and we have a path forward to do that. So it's just really about dotting Is and crossing Ts at this point as far as getting that submission into the agency. As far as review time lines, that's something that's out of our hands. That's something that the agency would determine. We think there's a clear medical need as evidenced by the rapid enrollment in the study and the execution of the study whatever the time lines will be, we'll work with the FDA is to get the drug approved to patients as fast as possible. We'll be ready to go as soon as they're ready to go.

Questions from the audience? You're entering a period where you could have 2 commercial products in 12 to 18 months. So what's going to be the key focus in 2026 in terms of your commercial infrastructure, medical education and prepping the market for these 2 products.

Yes. Two products coming forward. It's pretty cool. That's a pretty cool position to be in. And honestly, for the Nuvalent team, it's incredibly exciting. We've been so connected with the patients over the years, collaborating with them directly of how to get these drugs to patients. So for us to be in a position to deliver on that, it's honestly a dream that we can be in this position. So yes, our team is learning from all the others in this space. There are 15 years worth of drug development and the ALK-positive and ROS1 non-small cell lung cancer space. We can just learn what the others do, right? They were not inventing a new area here. We just have better molecules. Better molecules leading to better patient outcomes. So we can learn how the other drugs navigated all the different geographies, the U.S., Europe, Asia, et cetera, and try to figure out how to maximize the opportunity to deliver the drug to as many patients as possible as fast as possible. We've been building up our marketing team, our market access team, our commercial operations team. We're building our sales organization. We can learn how the others did such things. What went well? What didn't well. We've talked to many, many folks that have worked in this space for the last 15 years and brought those learnings into Nuvalent. We're not reinventing the wheel here. We're understanding what's been done. And can we do that or do it better? That's the strategy. Our team is very experienced in this space, and I'm really excited about that next phase of the growth of the company.

I have one more question, but any final questions from the audience? Jim, can you expand a little bit on NVL-330, the HER2 program that you have in lung? Historically, you've always said to me, hey, I'll give you an update, Anupam, when I have something important to say. When do you think we might get something on that? We've heard about this program background a lot, but...

Yes. I think you know me well, and you nailed my quote perfectly, Anupam. Yes, the way we -- I'm a scientist, I don't like to predict things. I'd like to run experiments and find the answers. So when we know the answer, that's one you'll know. I'm not going to predict when it's going to come. We've obviously made lots of progress. The trial we're working with many of the same physicians as the ROS1 and ALK program, right? Lung cancer patients these docs will treat HER2 ROS1 ALK. So there's a lot of interest in participating in this study just based on the experiences that physicians had with ALK and ROS1 and they see these HER2 patients. We don't like to guide to when the data is coming until we know for sure. It might be this year, but we'll really let the experiment play out. And when we know, we'll be sure to tell you. What's really exciting about the HER2 program is where to take it. And that's probably the most the probably the thing I would guide to you to look forward to the most, not just what have we learned in Phase I from a safety activity dose perspective. But where are we going? I think table stakes, the entry-level, we're going to go forward in lung cancer. That's what the program was designed for. There's a clear medical need for inhibiting HER2 exon 20 insertions with an index for not inhibiting wild-type EGFR, which is dose-limiting toxicity. And because it's lung cancer, you need excellent brain penetration. Those are chemistry problems. We have a chemistry company. We designed an excellent solution to address those chemistry problems, and that's a clear path forward for us. But beyond lung cancer, HER2 is an oncogene that drives many different tumor types. There's 2 decades worth of research and many drug approvals across small molecules, antibodies, ADCs for HER2-driven cancers. Well, the longer those patients stay alive, the more disease that they're going to have that spreads to the brain, right? What would be nice to combine it with is a selective HER2 inhibitor that broadly covers HER2 mutations and has excellent brain penetration. That's what NVL-330 is. So there's a clear opportunity here to consider going many different directions. Beyond just non-small cell lung cancer. So our team has been working on that. By the time we're sharing our dose and data. What is our path forward? Where are we going? Because there's clearly an opportunity to expand beyond the initial indication here.

Thank you, Jim.

All right.