Good morning and welcome to Nuvalent's conference call. At this time, all participants are in the listen-only mode. There will be a question-and-answer session after the prepared remarks. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Chelsea Lister, Senior Director of IR at Nuvalent. You may begin. Thank you all for joining us today. Earlier this morning, we issued a press release announcing top-line pivotal data from our ongoing ALKOVE-1 trial of Neladalkib for patients with ALK-positive non-small cell lung cancer. The press release and the slides that we will be using during today's call are available in the investor section of our website at nuvalent.com. On the call with me today is our CEO, Jim Porter. Our Chief Financial Officer, Alex Balcom, Chief Medical Officer, Dr. Christopher Turner, and Chief Development Officer, Darlene Noci, will join for the Q&A session. During this call, we will make forward-looking statements related to our current expectations and plans, which are subject to risks and uncertainties. We will also make certain forward-looking statements about the potential attributes and benefits of our product candidates and the format and timing of our development activities and clinical trials. Actual results may differ materially due to various important factors, including those described in the risk factor section of our public filings, including our Form 10-Q filed in October. These statements represent our views as of this call only and should not be relied upon as representing our views as of any date in the future. We undertake no obligation to publicly update any forward-looking statements. Let me now turn the call over to Jim. Thanks, Chelsea, and thank you all for joining us today. It's my privilege to represent the Nuvalent team today as we present top-line pivotal data from the ALKOVE-1 trial of our ALK-selective inhibitor, neladalkib. Over the past 15 years, tremendous progress has been made for patients living with ALK-positive non-small cell lung cancer. Before we dive into today's top-line results, it's worth grounding in the broader context of the current treatment landscape and where we see continued opportunity for patient impact. As detailed on Slide Three, Alectinib, a second-generation ALK TKI, is well established as a standard of care in the front line where it demonstrated a 79% ORR and median progression-free survival of 25.7 months by independent central review at the time of FDA approval. Patients progressing on Alectinib and other second-generation ALK TKIs often have ALK single mutations confirming resistance to therapy or brain metastases. Lorlatinib, a third-generation TKI, was designed with the goal of addressing the limitations of second-generation inhibitors through coverage of ALK single resistance mutations and improved CNS penetrance. Today, it is the only approved therapy with demonstrated activity following a second-generation ALK TKI, and it's the preferred second-line treatment option for patients following Alectinib. No approved therapies have demonstrated activity following treatment with Lorlatinib where a clear medical need remains. Experience with Lorlatinib has identified two additional limitations. First, insufficient coverage of ALK resistance mutations by Lorlatinib following prior treatment with second-generation TKIs has resulted in the continued presence of single ALK mutations and the emergence of compound ALK mutations conferring treatment resistance. In addition, Lorlatinib is a brain-penetrant dual-track ALK inhibitor, and CNS adverse events associated with track inhibition in the brain are observed in more than 50% of patients receiving Lorlatinib. The impact of these limitations can be observed in the modest activity of Lorlatinib for TKI pretreated patients. Following at least one prior second-generation TKI, Lorlatinib delivered an objective response rate of 31%-40%, with a median duration of response of 7.1-9.6 months. Experience with Lorlatinib has also clearly demonstrated that both activity and tolerability are of critical importance to physicians and their patients. Lorlatinib is approved for use in the front line and has demonstrated the potential for improved activity, reporting in 2024 that median PFS was not reached with five years of follow-up. However, many physicians, particularly in the community setting, continue to express reluctance to use Lorlatinib for their newly diagnosed patients due to the risk of CNS adverse events. We believe that due to this limitation, Alectinib remains the front-line market leader today. With this understanding of the current treatment landscape and limitations of available therapies, we saw three clear areas of opportunity for meaningful patient impact. First, for patients in the third line and beyond who have exhausted the available therapies, a compound that demonstrates any activity is needed to bring new hope to patients. For TKI pretreated patients who remain Lorlatinib naive, we believe there is opportunity to meaningfully improve on the 7.1-9.6 month durability response available today with Lorlatinib. Lastly, for TKI naive patients, we believe a therapy that could deliver comprehensive activity against drivers of disease progression, inclusive of ALK resistance mutations as well as brain metastases, and be well tolerated, would have the potential to demonstrate superiority to Alectinib and potentially become a new front-line standard of care. Turning to Slide Four, from these learnings, we designed Neladalkib with the goal of delivering the first and only ALK-selective compound designed to address the combined medical needs of hitting the ALK oncogenic driver, addressing or preventing ALK single and compound resistance mutations, having excellent brain penetrance, and avoiding TRK-related neurotoxicities. We confirmed these goals with the leading physician scientists who had developed the currently available ALK TKIs and continue to treat patients today, and set out to operationalize a global development plan that could evaluate Neladalkib across each of the three areas of opportunity we had identified. Our global development strategy, summarized on Slide Five, is anchored on two clinical trials, each designed with registrational intent. Our Phase I/II ALKOVE-1 study was designed with the potential to support initial indication for TKI pretreated patients, where we believe there is a clear medical need in the third line and an opportunity to differentiate from the second-line standard of care Lorlatinib in both durability and tolerability. Today, we're reporting top-line pivotal data from this trial and plan to discuss these data with the FDA at an upcoming pre-NDA meeting. Our ultimate goal is to establish Neladalkib as a best-in-class drug for all patients with ALK-positive non-small cell lung cancer, including those who are TKI naive. Each of the currently approved ALK TKIs achieved line-agnostic label expansion through demonstrating superiority over the standard of care at the time, Crizotinib, in a Phase III head-to-head trial. Consistent with this regulatory precedent, in July, we initiated ALKAZAR, our Phase III randomized controlled trial designed to evaluate Neladalkib versus the current standard of care Alectinib for TKI naive patients with ALK-positive non-small cell lung cancer. Global site activation and enrollment are ongoing. Turning back to the focus of today's data announcement, an overview of our ALKOVE-1 trial is provided on Slide Six. The Phase I dose escalation portion of our ALKOVE-1 trial enrolled heavily TKI pretreated patients, many of whom had exhausted all available therapies and was designed to determine the recommended Phase II dose. Preliminary data from the Phase I portion of the trial was first presented at the AACR- NCI- EORTC Symposium in 2023, with updated data presented at the European Society of Medical Oncology meeting in 2024. These data demonstrated preliminary clinical proof of concept supporting each component of our target product profile in a heavily pretreated patient population. Enrollment in the global open label multi-cohort Phase II portion of ALKOVE-1 began in February 2024, with a recommended Phase II dose of 150 mg once daily. The multi-cohort design allowed evaluation of Neladalkib within various pretreated subpopulations with the intention to demonstrate activity broadly across the TKI pretreated advanced ALK-positive non-small cell lung cancer population. Additionally, the trial included a cohort designed to enable preliminary investigation for patients with ALK-positive non-small cell lung cancer who are TKI naive, as well as a cohort for other ALK-positive solid tumors. We have been encouraged by the support from investigators and patients for our ALKOVE-1 trial, as evidenced by the robust enrollment shown on Slide Seven. In January of this year, we announced that we had enrolled 596 patients across the Phase I and Phase II portions of our ALKOVE-1 study. Following that update, we transitioned enrollment of adult patients with advanced ALK-positive TKI pretreated non-small cell lung cancer from our Phase II cohorts to our expanded access protocol. At the time of cohort closure on March 25th, 2025, 762 patients had been enrolled in ALKOVE-1. Enrollment remains ongoing in ALKOVE-1 for adult and adolescent patients with ALK-positive solid tumors other than non-small cell lung cancer and for adolescent patients with ALK-positive non-small cell lung cancer. As of the pivotal data cutoff date of August 29th, 2025, a total of 781 patients had been enrolled across the Phase I and Phase II portions of ALKOVE-1. This enthusiasm has been incredibly humbling and reinforces to us that a clear need remains for patients with ALK-positive non-small cell lung cancer. Importantly, it also enabled the inclusion of a substantial number of TKI-pretreated patients with ALK-positive non-small cell lung cancer in today's top-line pivotal data set. These patient populations are detailed on Slide Eight. Of the 781 patients with ALK-positive non-small cell lung cancer treated at any dose level by our data cutoff date of August 29 of this year, 656 patients received the recommended Phase II dose of 150 milligrams once daily and comprise our pivotal safety population. The pivotal primary efficacy analysis population includes 253 patients with measurable disease by blinded independent central review, or BICR. These patients must have received Neladalkib at the recommended Phase II dose by September 30, 2024, to allow for at least six months of duration of response follow-up for nearly all responders by the data cutoff date. Beyond our top-line data in TKI pretreated patients, we're also sharing preliminary data from 44 TKI naive patients with advanced ALK-positive non-small cell lung cancer from the Phase II exploratory cohort of ALKOVE-1. With that, let's dive into our top-line data results. ALKOVE-1 is a multi-regional trial with Phase I and Phase II patients enrolled across North America, Europe, Asia, and Australia. Key characteristics of the pivotal primary efficacy analysis population are described on Slide Nine. Overall, the population was heavily pretreated with a median of three prior lines of therapy and a range of one to 11 prior therapies. 51% of patients had received prior chemotherapy and 78% had received two or more prior ALK TKIs, of which 91% had received prior Lorlatinib. This population is unique to ALKOVE-1, as no other ALK studies have included Lorlatinib-experienced patients. Additionally, 19% of patients had a secondary ALK G1202R mutation, 17% of patients had compound ALK mutations, and 40% had active CNS disease at baseline. Notably, the pivotal primary analysis population also included 63 patients that were Lorlatinib naive, offering us an opportunity to evaluate Neladalkib's activity earlier in the treatment paradigm. All of these patients have received at least one prior second-generation ALK TKI with or without chemotherapy, of which 70% received prior Alectinib only. No patients in this subset received Crizotinib as their only ALK TKI, further highlighting the differentiating nature of ALKOVE-1 from other ALK studies in TKI pretreated patients. 19% of patients in the Lorlatinib naive population had a secondary ALK G1202R mutation, and 35% had active CNS disease at baseline. The top-line efficacy results observed in the overall TKI pretreated primary efficacy analysis population are detailed on Slide 10. Objective response rate, or ORR, and duration of response, or DOR, were evaluated by blinded independent central review. In the 253 patients that had received any prior ALK TKI with or without chemotherapy, the ORR was 31%, and the estimated probability of continued response, or DOR, rate was 76% at six months, 64% at 12 months, and 53% at 18 months by Kaplan-Meier estimate. The median DOR was not reached, which is encouraging as we think about the potential for durable responses even in the most heavily pretreated of patients. In Lorlatinib-experienced patients where no approved therapies had demonstrated activity, an ORR of 26% was observed, and the median duration of response was 17.6 months. It is our belief that any activity in these heavily pretreated patients who may have exhausted all available therapies indicates the potential for differentiation and improved activity in earlier lines of therapy. The overall TKI pretreated population also contains 47 patients with the most common ALK single resistance mutation, G1202R, which is present in approximately 35% of patients progressing on a second-generation ALK TKI. In this subset of patients, the ORR was 68%, and median DOR was not reached. The DOR rate was 84% at six months, 80% at 12 months, and 70% at 18 months by Kaplan-Meier estimate. Notably, responses were also observed in patients with compound ALK resistance mutations following treatment with two or more prior ALK TKIs. In these 43 patients, the ORR was 58%, and DOR rate was 69% at six months, with median not reached. These data support the potential for Neladalkib to provide an option for all TKI pretreated patients, including those who may have progressed on earlier lines of therapy with ALK resistance mutations. In addition, we believe that using a brain-penetrant TKI with broad coverage of ALK resistance mutations in earlier lines of therapy has the potential to extend the durability of response by preventing the emergence of on-target resistance in the periphery and in the brain. This belief is supported by the potential for differentiated durability observed in Neladalkib in TKI pretreated patients who are Lorlatinib naive, as outlined on Slide 11. In the primary efficacy analysis population, 63 Lorlatinib naive patients with advanced ALK-positive non-small cell lung cancer had received Neladalkib as a second-line therapy or beyond. As Lorlatinib is the only approved option with demonstrated activity after a second-generation TKI, we believe the evaluation of activity in this population is of high relevance for physicians and their patients. In this subset, an ORR of 46% was observed. The median DOR was not reached, and the DOR rate was 89% at six months, 80% at 12 months, and 60% at 18 months. We are highly encouraged by the durability of response observed in this Lorlatinib naive population. As I mentioned earlier, in the separate study of Lorlatinib for patients who had received at least one prior second-generation TKI, Lorlatinib delivered an objective response rate of 31%-40%, with a median duration of response of 7.1-9.6 months. Recognizing this is a small sample set, we're also encouraged by the activity observed in the 12 Lorlatinib naive patients with G1202R mutation. Here, the ORR was 83%, and DOR rate was 90% at six months and 77% at both 12 and 18 months. Similar activity was observed in the subset of patients that had received one prior second-generation ALK TKI with or without chemotherapy. In these 46 patients, an ORR of 48% was observed, with DOR rates at both 12 and 18 months of 74%. Overall, these findings support Neladalkib's potential to provide more durable responses for patients previously treated with second-generation ALK TKIs. Slide 12 shows Neladalkib's potential for durable responses in patients with CNS disease, looking first at the 92 patients with measurable CNS lesions by blinded independent central review at baseline that had received any prior ALK TKI with or without chemotherapy. The intracranial ORR was 32%, including 12 intracranial complete responses, or CRs, for a CR rate of 13%. The intracranial DOR rate at six months was 81% and 71% at both 12 and 18 months. Notably, this included CNS responses in patients who had previously received Lorlatinib. Lorlatinib has demonstrated what we consider to be impressive CNS activity, and we believe any signs of clinical activity in the CNS beyond Lorlatinib treatment is encouraging. In this population, Neladalkib was still able to deliver an intracranial ORR of 21%, with an intracranial DOR rate of 71% at six months and 55% at the 12 and 18-month landmarks. Intracranial activity was also observed in the subset of patients who were Lorlatinib naive and received Neladalkib as a second-line therapy or beyond. In these 24 patients, the intracranial ORR was 63%, including five intracranial complete responses, or CRs, for a CR rate of 21%. The intracranial DOR rates at 6, 12, and 18 months were all 92%. These data support the potential for Neladalkib to address active CNS disease both in earlier lines of therapy and beyond the brain-penetrant Lorlatinib, where no other TKI has demonstrated activity. As shown on S lide 13, Neladalkib was generally well tolerated, and the safety profile remains consistent with prior data. Treatment-emergent adverse events, or TEAEs, occurring in 15% or more patients were reported by preferred terms for 656 pooled patients with ALK-positive non-small cell lung cancer treated at the recommended Phase II dose. TEAEs above this threshold were ALT increased in 47% of patients, AST increased in 44% of patients, constipation in 28% of patients, dyschezia in 23% of patients, peripheral edema in 18% of patients, and cough and nausea both in 16% of patients. The most common TEAEs were transaminase elevations. Most were asymptomatic lab abnormalities and observed to be low-grade, transient, and reversible with dose interruptions or reductions. Preliminary data suggest increased incidence in less heavily pretreated patients. Therefore, we implemented enhanced monitoring and prompt dose interventions in the protocol for the Phase III ALKAZAR trial. Across the 656 patients treated in ALKOVE-1 at the recommended Phase II dose, dose reductions due to TEAEs occurred in 17% of patients. Importantly, treatment discontinuation due to TEAE continued to be low, occurring in 5% of patients. Our ultimate goal is to bring Neladalkib to all ALK-positive patients. Today, we are excited to also share the first look at preliminary data from the exploratory TKI-naive cohort of ALKOVE-1 that further supports the potential for Neladalkib to improve outcomes in earlier lines of therapy. Preliminary findings are highlighted in Slide 14 for the 44 patients treated in our exploratory TKI-naive cohort of ALKOVE-1, with a data cut-off date of August 29, 2025. For these patients, treatment with Neladalkib delivered an ORR of 86%. Durability of response ranged from 1.7-plus- 14.8-plus months, with a 91% DOR rate at 6 and 12 months and only two progression events among responders. Additionally, an intracranial ORR of 78% was observed in nine patients with measurable intracranial lesions, including four CRs for a CR rate of 44%. Intracranial DOR ranged from 3.1- 7 months with no CNS progression among intracranial responders. Taken together, we believe these data continue to support the potential for Neladalkib to be a generally well-tolerated therapy that can drive deep, durable responses for patients across the treatment paradigm. Turning to Slide 15, we're incredibly encouraged by these top-line pivotal data for TKI pretreated patients with ALK-positive non-small cell lung cancer and preliminary data for TKI naive patients. We believe these data confirm the clinical proof of concept previously reported in our preliminary Phase I data sets, including meaningful clinical responses for TKI pretreated and TKI naive patients, clinical activity in patients with key drivers of disease progression, and a generally well-tolerated safety profile consistent with Neladalkib's ALK-selective TREX-sparing design. Importantly, we believe these data demonstrate that combining activity against key drivers of disease progression with tolerability and convenience to keep patients on target therapeutic doses has the potential to translate to transformative durability across all lines of therapy, avoiding the need for treating physicians and their patients to choose between efficacy and tolerability. As encouraging as these results are scientifically, they also remind us of why we built this company. We founded Nuvalent with a commitment to patient impact. Today, it continues to be the value that defines who we are as a company. It reminds us that behind every data point is a person living with this disease, placing their trust in clinical research and inspiring us to push further every day. Earlier this summer, our team was fortunate to attend the annual ALK Positive Summit in San Diego, an event designed to unite patients, caregivers, healthcare professionals, and researchers in the fight against ALK-positive non-small cell lung cancer. During the meeting, we were privileged to witness the celebration of several patients reaching 10 years of survival with ALK-positive non-small cell lung cancer, a milestone that was once unimaginable. This is truly a testament to the tremendous work by the ALK-positive organization and the larger biopharma community's advancement of therapies that are making a meaningful impact for patients. Celebrating those survival milestones alongside others in the community was profoundly moving for our team, many of whom have built personal relationships with members of this community over the years. In every conversation with these inspiring patients, caregivers, and advocates, they continue to remind us that new treatment options are needed to help them spend more quality time with their loved ones. When we look at these top-line results reported today, we do not just see data. We see the potential for more quality time, for more days living well with cancer, and for more patients and their families to celebrate milestones of their own. We also see the courage and conviction of each one of the over 1,000 patients that has already chosen to receive Neladalkib through either our ALKOVE-1 trial or our global expanded access program, and the support of the ALK-positive community that has made this level of awareness possible. While our work is far from being done, I know I speak on behalf of the entire team when I say that getting to work on a program that has reached this many patients in so short a time is both inspiring and a true privilege. The work also extends beyond ALK, as we believe each of the clinical stage programs offers us the same opportunity to make a meaningful impact on the lives of patients. As summarized on Slide 16, today's announcement represents the culmination of a transformative year of achievements across our pipeline towards that goal. In just one year, we have reported the pivotal data for both of our parallel lead programs for ROS1 and ALK-positive non-small cell lung cancer and have submitted our first NDA application as a company in support of our investigational ROS1 inhibitor, Zidesamtinib, for TKI pretreated ROS1-positive non-small cell lung cancer. We plan to discuss the top-line data presented today with the FDA at a pre-NDA meeting with the goal of aligning on the NDA submission plan and timing to support a potential indication for Neladalkib in TKI pretreated patients with advanced ALK-positive non-small cell lung cancer. We also plan to present detailed study results at a future medical meeting. Beyond their initial TKI pretreated indications, global development paths are now in place to support potential line-agnostic label expansions for both Zidesamtinib and Neladalkib. We reported preliminary data for Zidesamtinib from the ongoing Phase II TKI-naive cohort of our ARIS-1 Phase I/II study, which is designed to support potential line-agnostic label expansion. In parallel, global enrollment of TKI-naive patients with advanced ALK-positive non-small cell lung cancer is ongoing in our Phase III ALKAZAR trial, which we initiated in July of this year. Beyond our predefined milestones for this program, we also presented preliminary data for Neladalkib in patients with ALK-positive solid tumors beyond non-small cell lung cancer. We are pleased to see that Neladalkib demonstrated encouraging activity across a diverse set of ALK-positive solid tumors, with a generally well-tolerated safety profile consistent with its ALK-selective TREX-sparing design. Enrollment continues in an ongoing Phase II cohort of our ALKOVE-1 study. Finally, we also continue to progress our third clinical program for HER2-altered non-small cell lung cancer. We presented new preclinical data for our third clinical stage program for HER2-altered non-small cell lung cancer at the AACR- NCI- EORTC symposium supporting NVL-330's potential for differentiated intracranial activity. Our Phase 1A/1B HER2-ICONIC study for NVL-330 is ongoing and progressing well, and we look forward to providing updates on that trial in the future. In closing, on Slide 17, our mission is to establish Nuvalent as a sustainable company with the ability to discover, develop, and deliver a portfolio of precisely targeted therapies for patients with cancer. For the past two years, our progress towards this mission has been guided by our OnTarget 2026 operating plan, which targets our first potential product approval in 2026. This plan is ambitious and requires consistent achievement of critical milestones across our pipeline. In this industry, the achievement of any one of the milestones we outlined for 2025, bringing a drug to the pivotal readout, submitting an NDA, or initiating a global Phase III trial, all while progressing a third program to clinical development, is no small feat. With today's announcement, we have successfully achieved all of the milestones outlined in our OnTarget 2026 operating plan for the second year in a row, and our goal of having a first potential product approval in 2026 is in clear sight. This is a truly remarkable accomplishment that was only made possible by the tireless dedication of our team, collaboration with physician communities and patient advocates, and most importantly, the patients and caregivers that participate in our clinical trials. Thank you for your support at this remarkable time in the evolution of our company. We look forward to sharing more in the months and quarters ahead as we continue building towards our mission of bringing new, potential best-in-class medicines to patients with cancer. This concludes our prepared remarks, and we would be happy to take your questions. Thank you. Ladies and gentlemen, we will now begin the question and answer session. To ask a question, you may press star followed by the number one on your telephone keypad. To withdraw your question, please press star followed by the number two. We kindly ask you to limit yourself to one question and one follow-up. Your first question comes from Brad Carino with Guggenheim. Please go ahead. Hey, good morning, Jim and team. Congratulations and great execution to this milestone. Two questions for me. First, I'd like to hear how you describe how you think this demonstrated Neladalkib profile can lead to an expansion of the TKI pretreated market opportunity, especially relative to historic ALK inhibitors that launch in that setting. Second, can you provide a bit more commentary around the liver enzymes and what you're hearing from investigators about the management of those relative to their experience with LFTs of Alectinib? Thank you. Thanks, Brad. Yeah, I'll take the first one first. How do we view the opportunity? This is a really, honestly, for the Nuvalent team, a privilege to work on a program like this. There are two things that jump out. One is just the massive enrollment, greater than 1,000 patients treated, overwhelming majority in the last 18 months. I'm not aware of a single Oncology trial in the history of Oncology drug development that has that type of enrollment. It is clearly supported by the patient community, the investigator enthusiasm. It speaks to the medical need, and it speaks that we're doing something right here. That really jumps out at us. The durability that we're seeing. We're able to drive durable responses across all lines of therapy. That is really saying something. It is speaking to the interest of this target. The tumors are highly dependent on ALK signaling. If you can hit the key drivers of disease and progression, meaning those resistance mutations, single or compound, get into the brain, and importantly, keep patients on therapy, that is the formula for driving these durable responses. That is really interesting because your question here is around what is the commercial opportunity. First and foremost, we care about making a meaningful impact for patients. With the massive interest in enrollment and the durability we're seeing, we think we have the opportunity to do that. We're also trying to build a business around this. More time, more durability means more time on therapy. More time on therapy means that we have the potential to grow the market. Across a couple of our programs here, ROS1 and ALK, we've shown durable responses in these patients, which means more time on therapy. The current ROS1 market with more time on therapy, we think could look something like the current ALK market, which is very interesting. Meanwhile, the current ALK market, which is around $2 billion currently, we think could significantly grow, maybe looking something approaching what the current EGFR market is. That's a game changer for Nuvalent. We're excited about the update. We're excited about what we're learning and the potential to grow these market opportunities. The second question you had was around the safety update. Chris, do you want to take that? Yeah, happy to. Thanks for the question, Brad. As we previously mentioned, transaminase elevations that are seen with Neladalkib are similar to what's seen with most TKIs and all of the ALK TKIs. They're typically just asymptomatic lab abnormalities that are picked up by blood draws. They're not even noticed by patients. When they do occur, they typically recur in the first one to two months on therapy. Because of this, Oncologists are really used to monitoring for this. Typically, they monitor weekly in the first month on therapy, and then every two weeks for the second and third month, and then typically follow up with monthly thereafter. It's something that Oncologists are really familiar with testing, and most patients do not even know that the labs are going up. All right. Operator, I think we are ready for the next question. The next question comes from Mark Frahm with TD Cowen. Please go ahead. Hey, thanks for taking my questions and congrats on the data as well. Maybe first off, just given the data you are showing today, can you maybe confirm what the kind of initial indication statement that you think you intend to seek with the FDA? Can you put the efficacy in that Lorlatinib-naive population kind of into the context of what the other times the FDA has granted single-arm accelerated approvals in a setting where there is some activity reported with alternative therapies? I will likely have a follow-up. Absolutely, Mark. Thanks for the question. The goal is to submit for previously treated ALK non-small cell lung cancer. Let me explain the rationale here. The general sequence that most physicians follow, they treat with Alectinib in frontline. When patients progress on Alectinib, the only drug that works is Lorlatinib. When they progress on Lorlatinib, nothing works. The overwhelming majority of the data we presented today are for patients in that third line plus setting where there are no available options. In Phase I, we showed deep durable responses. We received breakthrough designation in that setting. The data translated from Phase I to Phase II, we see deep durable responses in patients that previously received Lorlatinib, the second-line standard of care, which has a seven- to nine-month duration of response. We are seeing double the duration of response of Lorlatinib beyond Lorlatinib. That simply does not happen in Oncology drug development. When you give successive lines of treatment, the duration of response will go down. We are seeing double the durability of Lorlatinib beyond Lorlatinib, which really speaks to the attributes of Neladalkib and affirms our design goals for the program. Now, we also think this is an opportunity to pursue a second-line indication, meaning patients that have yet to receive Lorlatinib. In that setting, our drug is driving 46% response rates at the DOR landmark of 18 months. 60% of the patients are still in response. We are seeing Alectinib-like durability beyond Alectinib. It's really amazing. We're not really sort of real thrilled about that. As you know, in this space, Crizotinib used to be the standard of care, and Alectinib really changed the dynamic here by driving deep durable responses, took over as the standard of care, can drive a couple of years of durability. We're seeing that kind of durability in the previously treated setting. We think if we take that second-line data where we're driving these deep durable responses, and you combine it with that third-line data where nothing else works, we think we have a compelling argument to be made around a previously treated ALK non-small cell lung cancer indication. Okay, that's helpful. Maybe to follow up on Brad's earlier question on the liver testing, just in the Phase III now, can you maybe describe the testing paradigm for patients and how it fits into Chris? I think you described a minute ago what's essentially in the label for Alectinib. I mean, is that the protocol that you're now following, or is it something different? Yeah. A lot of physicians even do beyond what's in the label for Alectinib. As I described, it's pretty common to do actually monthly or, sorry, weekly in the first month, and then every two weeks for months two and three, and then monthly thereafter. I think what we did and what we've implemented is some additional blood draws early in treatment to be able to detect and intervene earlier to ultimately reduce the number of higher-grade events and minimize the impact to patients in the long run. Thank you. The next question comes from Laura Prendergast with Stifel. Please go ahead. Hey, guys. Congratulations on the data. I want to zone in on that comment you had in the press release that over 1,000 total patients across the Phase I have been treated with Neladalkib. Subtracting out the Phase I/II patients, it seems like you have well over 200 patients enrolled in the EAP. Can you provide any additional commentary here, whether these patients are coming from U.S. or ex-U.S., and how they could convert to commercial patients upon approval? Yeah, thanks, Laura. The program is just between the ALKOVE-1 and the expanded access, there's just been a lot of interest in Neladalkib. It has a differentiated profile. Physicians are excited about it. I think they're having good experience with their patients. The patient communities are excited about the opportunities. We wanted to make Neladalkib available for all patients that need it. We significantly over-enrolled the ALKOVE-1 study. The original protocol called for around 300 patients or so. We enrolled more than double that, 781 patients, because of the enthusiasm for the trial. Honestly, I think all of us at Nuvalent recognize this is like a career-defining opportunity for us to work on a program like this. I am just proud of the team rising to the occasion to meet that challenge. The expanded access was something we put in place because we wanted to continue to provide access for patients with Neladalkib, but we wanted to work on closing the actual non-small cell lung cancer cohorts in the Phase II study. I think your math checks out. Yes, it is well north of 200 patients that are on the expanded access program. This is a global expanded access program, so it is across geographies North America, Europe, Asia. We are seeing excellent interest across all those geographies. To your point about conversion, maybe Alex, you want to speak to that? Sure. Yeah. On the conversion, we would expect that upon potential approval in the U.S., those patients on the EAP would convert to paid drugs. Got it. One follow-up. Are these patients exhausting standard of care, both Alectinib and Lorlatinib, or is it possible that some of these patients have moved on to the EAP access because of tolerability issues with CNS issues with Lorlatinib, for example? Yeah. Thanks, Laura. The protocol is typically for expanded access program, the patients do have to have exhausted available options, or the physician has deemed the patient not acceptable for any other approved therapies. I think that addresses where we're going. If a patient was intolerant to another therapy, then yes, they would be eligible for the expanded access program. Thank you. The next question comes from Anupam Rama with JP Morgan. Please go ahead. Hey, guys. Thanks so much for taking the question and congrats on the update. Just a question on the 17% of patients that had dose reductions. Were those mostly due to transaminases? I guess, what type of activity was observed after the dose reduction? Thanks so much. Yeah. Maybe I'll start on the activity, and then Chris, you can speak to the dose reductions. One thing about the Neladalkib profile, what we learned in Phase I is we had activity across the entire dosing range, Anupam. We chose 150 mg as our recommended Phase II dose. If you go back to our Phase I data, you can see that our responses were pretty consistent across all dose levels. The 100 mg dose level, so the dose level below 150, also provides excellent target efficacy threshold coverage. It does allow us to do dose reductions and still maintain patients at appropriate target efficacy thresholds. I think that really helps with the activity. Chris, you want to speak to the second part? Yeah. Happy to. Overall, we're very encouraged by the overall low rate of dose reductions of 17% regardless of the adverse event. I think you were specifically asking about the transaminase. There's only 11% of the patients who had dose reductions due to transaminases and only 3% discontinued due to that. This is very similar. If you look at something like Alectinib, which is considered a well-tolerated drug, they have 23% dose reductions and 6% discontinuations. We are very pleased with our safety data overall. Thanks so much for taking our question. Thanks, Anupam. The next question comes from Andrew Barons with Luring Partners. Please go ahead. Thanks. Congrats on the big milestone for the company and also for ALK patients. Seems the pre-market may be reflecting some concern, the modest erosion in efficacy between this trial and the prior Phase D. I think there's some key differences, like the fact that 1B excluded concomitant oncogenic drivers, and also the 1B was local reads versus BICR in this trial. Do you actually have any data from this trial that more closely reflects the 1B results for an apples-to-apples comparison? We noticed that all the prior ALK drugs receive broad labels that allowed usage in patients intolerant to prior ALK agents. Wondering if you think that's still something the current FDA would consider, and if so, the potential implications. If I could just sneak a third one in about the LFTs. I think you said in the slide deck that the rate was higher in naive patients. That seems a bit counterintuitive, but does it suggest that it goes down with time and is not cumulative? Yeah. Thanks, Andy. So three questions there. First of all, the differences between the Phase I and II, I think what the general theme is we're seeing durable responses across all lines of therapy in the Phase II. Regarding the specifics of the patient populations, in Phase II, as is typical, you would report activity by blinded independent central review. It's a higher bar than a Phase I, which is investigator-assessed for activity. Another difference, as you pointed out, there are about 10% of the patient population, so of the 253 patients, 25 that had other oncogenic drivers that were included in the analysis patient population. In Phase I, by protocol, those were not included in the analysis patient population. These patients could have had other oncogenic drivers like MET amplification, MET mutations, BRAF, KRAS, G12C. We do see some activity in those patients, but you can imagine it's a harder patient population to treat because they have multiple oncogenic drivers. What is likely going to be needed for a patient like that is eventually combination therapy. Your second question around, are patients, is the registration strategy around a broader label progressed or intolerant? I think you're right to point out that other ALK drugs received such an indication where patients that had progressed or were intolerant to Crizotinib, that was the original indication statement for some of these second-generation ALK TKIs. We certainly noticed that and understand that. I think that the data we generated clearly supports that our drug can drive durable responses regardless of the line of therapy. I think we have a lot of interesting data to share with regulators around a broader previously treated ALK indication. The third question was around the naive patients. Chris, do you want to take that? Yeah. Just to clarify too, I think what we had indicated was preliminary data suggests increased incidence in less heavily pretreated patients. It's just not the TKI naive only. As we pointed out earlier, this is a heavily pretreated population with one to eleven lines of therapy. And what we noticed when we just look across all lines of therapy, that there's a little bit of a trend with the less heavily pretreated patients across the board. We have a number of hypotheses there. We don't necessarily want to get into speculation at this point, but it is an interesting phenomenon we're noting. Thank you. Congrats again. Thanks, Andy. The next question comes from Charles Zhu with Lifesight Capital. Please go ahead. Hey, everyone. Congrats on this update, and thanks for taking our questions. My first one is a little bit of a semi-follow-up to Andy's question. What's the proportion of ALK-mutant versus ALK-wild type patients that you'd expect to see out in the real world? I'm mostly asking you because it seems like you had a lot more mutant patients last year at ESMO at 56% relative to today's 36%. We see, for example, the ORR and DOR differences between these two populations, not only for you guys, but also for Lorlatinib. I wanted to get your sense there in terms of real-world proportions. Thanks. Thanks, Charles. We believe the data supports post-Alectinib, around half the patients are progressing with ALK mutations. That can range from the ALK G1202R mutation, the most common, the L1196M gatekeeper mutation, the I1171X mutations. Neladalkib was designed to address all these mutations. In addition, Neladalkib was designed to address compound mutations. Compound mutations occur because of Lorlatinib's inefficient coverage of the first mutation. The second mutation starts to grow in, patients will progress. Our drug was designed and optimized to cover those mutations. I think that's why we can see durable responses regardless of the line of therapy, even beyond Lorlatinib. I think that range of ALK mutations overall in previously treated patients, it's going to be somewhere in that 40%-50% range. I do not think we have a large enough data set to really get more granular than that, Charles. I think our data update here suggests that there are a decent amount of patients with ALK mutations, and our drug is working quite well in those patients. Excellent. Congrats again, and thanks for taking the question. Thanks, Charles. The next question comes from Joshua Schimmer with Cantor. Please go ahead. Thanks for taking the question. Congrats on the update. Just want to dive into the expanded access program a little further. Can you discuss the cadence of enrollment of patients in that program, specifically in the U.S., whether there are any restrictions to the number of patients you can enroll in the U.S., and are these patients all TKI pretreated? Thank you. Thanks, Josh. Yes, all TKI pretreated. As part of the expanded access program, patients would have to have had exhausted available options, or physicians have deemed them not appropriate for the available options, right? They might have taken Alectinib and Lorlatinib, they've progressed on both, or they might have taken Alectinib, perhaps Lorlatinib is not an appropriate option for them, and a physician could put them on. This is enrolling across all geographies. It's enrolling well across all geographies, including in the U.S. I don't want to know if I don't think we can get into more specifics on what the enrollment is by geography other than it's going well across all. Okay. Are there any restrictions into the number of patients that ultimately can enroll? No restrictions. No restrictions. Okay. Thank you. The next question comes from Rick Lowe with Goldman Sachs. Please go ahead. Hey, guys. Congrats on this achievement. In your TKI pretreated patients, have you looked specifically at only patients who were Lorlatinib pretreated, and what do the results look like? In the past, I think you guys broke out those details. Curious how that compares to your 31% overall and the 32% intracranial OR. I have a follow-up. Thanks, Rich. Yeah, there are 190 patients that received prior Lorlatinib. That is a patient population where nothing else works. 26% of these patients responded, and their median duration of response was 17.6 months. That's what really stands out to us. That's double the durability of Lorlatinib beyond Lorlatinib. That just doesn't happen in oncology drug development. I'm not aware of really any examples where that happens. We also saw really interesting intracranial activity beyond Lorlatinib. Lorlatinib is one of the gold standards as far as brain penetrance. Any activity in the CNS beyond Lorlatinib is encouraging. We saw roughly 21% of the patients that had activity in the intracranial compartment, an ICOR rate of 21%, and those responses were durable. Over half the patients still in response at that year-and-a-half landmark. Very encouraging data beyond Lorlatinib. Was there a second part to that question, Rick? I'm drawing a blank here. No, that was it, but I have another question. In the exploratory cohort of the 44 TKI naive patients, what was that median follow-up across these patients? Do you expect the results to mature further, or are they fully mature, and how do you think this compares to Alectinib's and Lorlatinib's data so far? Thanks. Yeah. The 44 patients in the TKI naive cohort, so this is an exploratory cohort. We think we captured the update across the entire population of follow-up was 11.6 months. I do not think we broke it out specifically for the TKI naive patients, so I cannot report on that data today. This is an early look. We expect that Neladalkib could drive years of durability for these patients, right? At the 12-month landmark, 91% of these patients are still in response. We hope they have many, many more years to go on Neladalkib. We'll be following these patients for a long period of time. What stands out from this update? 86% response rate, 79% intracranial response rate for those patients with complete responses, only two progression events total among the 38 responders. Very encouraging data. If we map this out, this looks as good or better than what a drug like Lorlatinib can do in this setting. I think we all know that Lorlatinib has the potential to drive deep durable responses in this setting. The challenge with Lorlatinib has been the off-target toxicity. What we're seeing with Neladalkib is we're not seeing those off-target track-related CNS events. Therefore, potentially keep patients on therapy for long periods of time and drive deep durable responses, create considerable value for patients with ALK-positive non-small cell lung cancer. Yeah. Sorry, I meant to ask, do you think the ORR could continue to mature over time? Or do you think the ORR is pretty much mature at this point? There's a potential for some of those patients that are still on the drug that have yet to have a response could convert to a response. So it could get slightly better, yes. Great. Thank you. The next question comes from Kelsey Goodwin with Piper Sandler. Please go ahead. Okay. Good morning, everybody. Thanks for taking my question, and congrats on the data. Two quick ones from me. First, I guess, could you just provide some more details on the dose reduction? I guess, to what dose are they reducing to? How many reductions are they getting? Secondly, obviously, very impressive enrollment in the Phase I,II, and expanded access program. Any commentary on the ALKAZAR trial enrollment? Are you seeing the same level of physician enthusiasm there? Thank you. Thanks, Kelsey. The dose reduction, we start at 150, and the dose reduction is to 100. As we mentioned before, in the Phase I, we saw excellent activity and coverage of the target FDA threshold at 100. That was one of the reasons we chose 150 as our dose. As you can imagine, patients with ALK-positive non-small cell lung cancer are likely to have adverse events associated with their disease. Having a flexibility of a dose reduction that still provides excellent target coverage is an advantage for Neladalkib. As far as the enrollment in ALKAZAR, it is going well. It is going according to plan. We are going to enroll this across North America, Europe, Asia, and Latin America. There are 160 sites that we are planning. The team's doing incredible work getting these sites open. We have broad enthusiasm from investigators in the patient advocacy communities that we collaborate with. We think this trial is going to enroll well, but no specific update we are providing today on what that enrollment metrics are. We will look to maybe do that in the future. Understood. Thanks so much. Thanks, Kelsey. The next question comes from Chris Raymond with Raymond James. Please go ahead. Hey, this is Sam on for Chris. Thanks for taking our question. Congrats on the data. One clarification and one question for us. In the press release, I noticed that you said the median duration of exposure was six months from the whole 650-patient safety cohort. Could you just clarify what the duration of exposure was for the efficacy cohort that you were commenting on today? I do not think I see this spelled out in the data. Could you comment on the response rate that you're seeing in just the patients who have only had one prior TKI? And do you see any differences in response depending on what that first TKI was? Thank you. Thanks, Sam. So yeah, just a clarification between duration of median follow-up as compared to duration of exposure. I think you cited the six months. That was from the broader safety population. There are roughly 650 patients, six months of follow-up there. For the analysis patient population, 253 patients. It was a little over 11 months for median follow-up for those patients. Remember, we do a look-back and cut the analysis patient population to have all patients have at least six months of DOR follow-up, and that's why we get more time on study for those patients as compared to the full safety set, which includes all patients with non-small cell lung cancer that receive the recommended Phase II dose. As far as the one prior TKI, we saw in that patient population that have yet to receive Lorlatinib, I think we have called out that all those patients received at least one prior second gen. Some of those patients would have received Alectinib plus Crizotinib, some of them Alectinib plus Brigatinib, some of them maybe Brigatinib plus Crizotinib, and all the combinations thereof. The response rate there was 46%. 60% of those patients were still in response at that year-and-a-half landmark, which really is impressive. In that same slide, we did call out a subset that received only one prior second-gen TKI. So 44 of these patients received Alectinib. Two of these patients received Brigatinib. I think the response rate was 48%. And 74% of these patients were still in response at a year-and-a-half landmark. Again, that's incredible durability in a previously treated patient population. It's looking more or even better to what Alectinib can do in the front line. We're seeing that in a patient population beyond Alectinib, which really speaks to the attributes of Neladalkib here. Great. Thank you. Thank you. The next question comes from Ed Serdaro with Berkeley. Please go ahead. Thanks for taking the question. Congrats on the data here. Maybe if you could comment on what you know about the real-world duration of therapy for Lorlatinib versus what's previously presented in the literature and your expectations for the durability for Neladalkib in the real world based on sort of those observations. Have the FDA commented any particular subgroup of the data that it would like to see in terms of sort of efficacy, durability? For example, look at the Lorlatinib experience population where there are no approved therapies and if there's special interest from the FDA in maybe that subgroup or other subgroups that you'd want to call out. Thank you. Thanks, Edser. The Lorlatinib duration response post-Alectinib is about seven to nine months. The PFS is even lower. I think it's around six months in that patient population. You can imagine in the real world, it might be even lower. What we hear often from physicians is the challenges with Lorlatinib is keeping patients on therapy. ALK non-small cell lung cancer, unfortunately, is a disease that commonly impacts folks when they're younger. They're 30, 40, 50 years old. They're in the prime of their life. They have professional milestones. They have personal milestones. Lorlatinib is a difficult therapy to tolerate. Many patients we hear from directly are scared of Lorlatinib. They do not want to go on that treatment. They want more options that they can stay on therapy and still live their life, still do their job, still be part of their family, and not have their therapy impact or dictate their day-to-day. That's one of the reasons that we came up with this profile, working with physicians that had direct experience with Lorlatinib and the limitations that drug has in the previously treated ALK-positive non-small cell lung cancer setting. We are not seeing those track-related neurotoxicities. We are seeing patients stay on therapy. We're seeing durable responses, even in patients that have previously received Lorlatinib or in patients that have yet to receive Lorlatinib. I think that really speaks favorably about us being on the right track here with Neladalkib. Your question about what do we expect the duration of therapy for Neladalkib to be in the real-world setting, difficult to know at this point. We obviously are encouraged by the massive enrollment we're seeing and the durability across all lines of treatment. We think that would translate well to time on therapy in the real-world setting, but that's to be figured out going forward. As far as what our registration strategy is, maybe Darlene, you want to take that? Yeah, sure. Thanks for the question. We're super excited to share the data with the FDA and the next steps for our program as part of an upcoming pre-NDA meeting. We're planning to seek an all-pre-treated indication based on this ALKOVE-1 study. As far as details regarding subgroups, we don't disclose the details of our discussions with the regulators. Again, we're super excited to be where we are today and for an upcoming discussion with FDA around the data. Great. Congrats again. Thank you. The next question comes from Robert Roger Song with Jeffries. Please go ahead. Hey, team. This is Nabil on for Roger. Congratulations on the updates, the trial results. Just had two questions. Looking at that exploratory naive cohort and those two progression events and 38 responders, that's about a 5% rate. How do you contextualize that? And again, being that it's preliminary, how do we look at that when we look at escape mutations from other ALK TKIs? And then I had another follow-up. Thanks, Nabil. Yeah, listen, the TKI naive cohort, it's early, right? We're reporting DOR landmark at one year. We want these patients to have years of progression-free survival. Only two progression events of the 38 responders, it's promising. It looks as good or better than Lorlatinib. That's saying something, right? We're thrilled about that. We also predicted that. We predicted this drug would work better than all the other ALK drugs. It has a profile that the other ALK drugs do not have. It is the first and only drug that can hit the oncogenic fusion, hit the mutations, single and compound mutations, has excellent brain penetrance, and importantly, can keep patients on therapy because we are not hitting those off-targets that drive dose-limiting toxicities. We are not surprised that it looks great, but we are actually pretty happy to see it. Great. Thanks. You mentioned you will have updated data at a medical conference. Would that include more mature data cutoffs? Would we also see subsets of second-line versus third-line Lorlatinib experienced? How do you see the safety profile in an updated set? Would you see something similar, or? Thank you. Sure thing, Nabil. Typically, what is done here in a pivotal data set is you go discuss that data with regulators. Ideally, these will be the data that we submit for an NDA. A medical meeting presentation in the future will likely be the same data cut. There is an opportunity to present more data as we did for our ROS1 program. Just to put it in context, we presented top line for our ROS1 in June of this year. At the WCLC meeting in September, we presented at the presidential symposium, same data cut, just a more fulsome data presentation at the medical meeting. I think that that same blueprint probably makes sense for the ALK program as well. Thank you, team. Just if I could sneak one more question in on that safety profile, how do physicians and investigators look at that AE profile when it comes to the CNS-related AEs versus an incremental increase in LFTs, which, as you mentioned, are common in this class? Yeah. I would say the best evidence how investigators feel about the drug is that we've enrolled over 1,000 patients in the last 18 months. Again, I would challenge it. I've talked to several of our analysts about this. Can we find another trial in all of oncology drug development in the history that has this type of enrollment? Keep in mind, this is a rare tumor type. I think that tells you all you need to know how physicians feel about Neladalkib. This is a differentiated profile. We know the patients are excited about it. I think that's why our trials enroll so well. I think that's the best evidence that we can support your question. Thank you. The next question comes from Charles Ramakanth with Stevens. Please go ahead. Thank you very much. This is RK from H.C. Wainwright. Congratulations, Jim and team. Couple of quick questions. I'm just thinking through the median DOR, especially in the second-line setting, which is Lorlatinib naive patients. What's the longest these patients have been followed to date? I understand you are not, the data is not matured enough to show the median DOR. The second question is, based on what you're seeing in the exploratory cohort of 44 patients in the TKI naive cohort, what would your expectations be for the ongoing ALKAZAR? Thanks, RK. The first question was around what's the longest these patients have been followed. Keep in mind the analysis patient population includes any patients from the Phase I or Phase II that have non-small cell lung cancer that were treated at the recommended Phase II dose. I mean, this trial only started the Phase I in June of 2022. Just a little over three years total in the history of this oncology development program. No patient could have been followed longer than that because that's when the trial started. We don't have it broken out of how many of the Phase I patients started at the recommended Phase II dose that are in the analysis set. I wouldn't be able to specifically answer your question. The Phase II started in February of last year. You can see that we saw massive enrollment right from that get-go. Most of those patients are in that time frame where they started between February and August of last year. The second question was, what do we expect as far as durability on ALKAZAR? We expect to give years of progression-free survival. That's the goal here. Alectinib is a game changer in the ALK space. Crizotinib was the original standard of care. It drove about 12 months of durability for patients. It created about a $500 million market at its peak. Alectinib came along, and it did great things for this community. It doubled the durability of Crizotinib, right? And it quadrupled the market. We're looking to do something like that compared to Alectinib. We think that with 50% of the patients progressing on Alectinib, that's not good enough, right? And ALK-positive non-small cell lung cancer patients deserve something better. Neladalkib has that profile. It has been designed to keep patients on therapy for extra years. That would be a game changer for that patient community. And it will represent a very compelling opportunity for Nuvalent. Thank you. The next question comes from David Dye with UBS. Please go ahead. Thanks for taking my questions. I'll make some graduations on the data here. Two quick ones from me. First, just thinking about the funding strategies, can you maybe just give us some sense around what are some of the key questions you need to discuss with the FDA to get the second-line Lorlatinib naive on the label? Secondly, just regarding the liver enzyme elevation, you're now implementing more monitoring for the ALKAZAR trial. How do you think the drug reduction percentage will evolve in the Phase III ALKAZAR trial? How do you think this might impact survival outcomes compared to Alectinib? Yeah. On the second, I think the second question first, David, as we mentioned, the dose reduction provides excellent coverage of ALK and ALK mutations. We're not concerned at all about any dose reductions. We're seeing durable responses even in the Phase I across the entire dosing range. This was a luxury we had with a Neladalkib profile. Patients with lung cancer will have dose reductions based on their underlying disease. To have multiple dose levels that can cover that target threshold is an advantage. Neladalkib has that. Regarding the filing strategy, as Darlene mentioned, we're going to bring this data to the regulators to discuss a broader previously treated ALK indication. Third line, where nothing else works, we have breakthrough designation. Second line, where Lorlatinib is the standard of care, and we can drive significantly longer, more durable responses than Lorlatinib, excellent CNS activity, keeping patients on therapy. I think the collated data, we think, presents a compelling argument around a broader previously treated ALK non-small cell lung cancer indication. Thank you. Our final question comes from Colleen Cussie with Baird. Please go ahead. Great. Thanks for taking our questions. Congrats on the updates today. I realize this is an early top-line look at the data, but can you speak to any indication of benefit for those patients that did not achieve an ORR? Can you just speak quickly to the filing strategy for global territories, any timelines for Europe, and whether you'd expect a broad label there as well? Thank you. Thanks, Colleen. These trials were designed to support global registration, right? We certainly have an interest in getting these drugs approved for all patients across all geographies. I can tell you it enrolled well across all geographies. We intend to, once we discuss with the FDA, also follow that up with the global regulators. That is the strategy there. As far as your first question, is there benefit for patients that did not actually have a response? Yes. You can imagine that there are often going to be patients that do not have at least 30% tumor reduction, which is the RECIST 1.1 response criteria, but still derive benefit for the therapy. You can imagine, particularly in a very advanced patient population where patients have progressed on so many lines of therapies, that there could be heterogeneous disease. Not all the disease is driven strictly on ALK at that time. It is an opportunity to still have benefit for patients, but not actually hit that 30% reduction threshold. Those patients are likely to continue on therapy, often that is measured by an endpoint progression-free survival. This update did not include PFS. We really tailored it around how regulators view a single-arm Phase II data set. They want to know, do you shrink the tumors and for how long and what the safety profile is? That is ORR, DOR, and safety. As you might know, in the ROS1 program, that is how we tailored our top-line update. At medical meetings, we considered PFS for investigators. Maybe more to come on that in the future. Big picture, we are excited about what we are seeing on the durability for these patients across all lines of therapy. Thank you. That concludes our question and answer session. I would like to turn it back to Jim Porter for closing remarks. Great. Thank you all for joining us today. We are really proud of the progress we have made across our pipeline and appreciate your continued support of Nuvalent. We look forward to speaking with you in the weeks and months ahead. Thank you, presenters. This concludes today's conference call. Thank you all for joining. You may.