Good afternoon and welcome to the Nuvation Bio First Quarter 2025 financial results and business update conference call. Please be advised that today's conference call is being recorded. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for questions. I would now like to turn the call over to J.R. DeVita, Executive Director of Corporate Development and Investor Relations at Nuvation Bio. Please go ahead. Thank you, Operator, and hello to everyone joining us today. We recently issued a press release announcing the U.S. FDA approval of taletrectinib, now known under the branded name Iptrozi in the United States. Iptrozi is a next-generation oral tyrosine kinase inhibitor, or TKI, for advanced ROS1-positive non-small cell lung cancer, or NSCLC. This press release and an updated corporate presentation are available on the investor section of our website at nuvationbio.com. A replay of today's recording will be available shortly after the conclusion of this call. Joining me today are Dr. David Hung, our Founder, President, and Chief Executive Officer, Philippe Sauvage, our Chief Financial Officer, and Kerry Wentworth, our Chief Regulatory Officer. Today's discussion will focus on the FDA approval of Iptrozi, our launch plan, and next steps as we bring this important new medicine to patients. We will be making forward-looking statements on this call, which are based on our current expectations and assumptions. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the U.S. Securities and Exchange Commission. Now, I'll turn the call over to Dr. David Hung. David. Thanks, J.R., and thank you all for joining us today. This is a truly exciting moment for Nuvation Bio and, more importantly, for people living with ROS1-positive non-small cell lung cancer. Today, they have a new treatment option. With the U.S. FDA approval of Iptrozi, Nuvation Bio is a commercial-stage company launching what we believe is a best-in-class ROS1 inhibitor and the first of several differentiated medicines in our broad pipeline. We know that behind every data point used to achieve this approval is a person, a parent, a partner, a colleague whose life has been disrupted by this aggressive disease. For many of them, the emotional and physical toll can be overwhelming. This approval means patients now have access to a new targeted therapy designed specifically for their form of lung cancer, with the potential to hold their disease at bay and help them focus more on moments that matter. Before I talk about the clinical data and what this means for the company, I want to begin with sincere gratitude. In addition to the patients, I would also like to thank their families, the investigators, and the clinical teams who made our studies possible. Furthermore, we want to acknowledge the Herculean efforts of the FDA reviewers and inspectors assigned to this high-priority NDA submission. As you know, Iptrozi had been granted breakthrough therapy designation by the FDA in both the first and second-line settings. No other drugs currently in development have this designation. Iptrozi, accordingly, received priority review for its NDA submission, and we are so pleased to receive approval weeks prior to our PDUFA date of June 23. Finally, I would like to thank the dedicated team at Nuvation Bio for their relentless focus, persistent passion, and unwavering commitment that resulted in today's announcement. At our core, Nuvation Bio has always been motivated to challenge the status quo in cancer treatment, especially in some of the hardest-to-treat cancers. This approval is a meaningful step toward that goal. As mentioned previously, ROS1-positive lung cancer is a particularly aggressive disease. It is a rare, genetically defined form of lung cancer, and for the people it affects, the burden is significant. Most are young, on average about 50 years old, and are otherwise healthy people who have never smoked. Despite having targetable mutations, they unfortunately face a high risk of disease progression. To address this unmet need, we developed Iptrozi, a next-generation highly selective ROS1 TKI, now approved for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer. Iptrozi was designed to address the real-world challenges patients face when battling this disease, especially when it comes to durability, tolerability, and the ability to shrink tumors in the brain and treat the most important pathways through which these cancers develop resistance to other therapies. Now, let us walk you through the registrational data set that was the basis for the FDA's decision. The approval of Iptrozi is supported by one of the largest global clinical trial programs in ROS1-positive lung cancer to date, including a safety database of more than 400 patients. This database continues to grow. Since NDA submission, we have enrolled additional patients in the global Trust 2 study, which now includes more than 135 patients from North America and Europe. As you know, the full results from the Trust 1 and Trust 2 studies were recently published in the Journal of Clinical Oncology, or JCO. As summarized in this publication, in the Trust 1 and Trust 2 studies, across different lines of therapy, Iptrozi showed consistent durable responses, strong intracranial activity, and was generally well tolerated, including a low rate of discontinuation and tolerable central nervous system, or CNS, effects. In a poster presentation at the ASCO conference, we reported that the efficacy and safety profiles observed in Trust 1 and Trust 2 were remarkably consistent across demographics and regions, reinforcing the applicability of Iptrozi data across diverse patient populations. While our JCO publication and our initial NDA submission reflected pooled results from the Trust 1 and Trust 2 studies, the Iptrozi label presents the results from each study individually. This was based on discussions with the FDA, mainly driven by differences in the median follow-up between the two studies. As a reminder, Trust 2 was initiated over a year after Trust 1. In addition, the label reflects more mature data cutoffs than prior presentations, reinforcing the strength of the findings now shown separately. Now, I will discuss the latest data as presented in the Iptrozi label unless otherwise noted. In Trust 1, Iptrozi achieved a confirmed overall response rate, or ORR, of 90% in patients who did not previously receive a TKI treatment, also known as TKI naive. In addition, the median duration of response, or DOR, was not yet reached, with a median follow-up of response of 40 months. The longest DOR observed was at 47 months and is still ongoing. These findings were reinforced by the Trust 2 results, with a confirmed ORR of 85% in TKI naive patients. The median DOR was also not reached in patients enrolled in the Trust 2 study. However, this information is not presented in the label given the shorter follow-up time. The longest DOR observed was at 30 months and is still ongoing. We believe that the results in TKI naive patients in Trust 1 and Trust 2 are striking. You've all seen the median DOR and PFS for taletrectinib in our previously mentioned JCO publication. That data set was based on a data cutoff date of June 2024, nearly one year ago. Our label discussions with FDA were based on a more recent data cutoff of October 2024 with respect to duration of response. As a result of the more recent data cutoff, Iptrozi's response durability metrics in our label are not yet reached in the TKI naive patients. We're pleased with the resulting label, which we believe reflects Iptrozi's powerful and durable efficacy, and we anticipate further label updates as data mature with more follow-up time across both trials. As you know, Iptrozi's very first clinical trials were initiated a little over nine years ago. As an example of what Iptrozi's durability of responses have meant for TKI naive patients, in a recent follow-up of the 15 patients dosed in one of the earliest-ever studies for Iptrozi, a phase one study in the TKI naive setting, one patient has now exceeded eight years of treatment, and two others have now exceeded the nine-year mark, all three patients still continuing to receive Iptrozi. In addition, one of the patients on therapy for nine-plus years currently has no evidence of residual tumor, otherwise known as a complete response. The fact that 20% of our 15 patients with a cancer as aggressive as ROS1-positive non-small cell lung cancer are still continuing to receive Iptrozi, approaching a decade from treatment initiation, is something that I personally have not seen in my career as an Oncologist and biotech executive. We look forward to future follow-up data to see how long the benefits of Iptrozi might further extend in this setting. Robust results were also observed in patients previously treated with a ROS1 TKI, also known as the TKI pretreated population. In Trust 1, TKI pretreated patients who received Iptrozi achieved a confirmed ORR of 52% and had a median DOR of 13 months, with median follow-up of 33 months. In Trust 2, our predominantly Western study, TKI pretreated patients treated with Iptrozi achieved particularly impressive results, including a confirmed ORR of 62%. While not included in the label given the shorter follow-up time, the Trust 2 data submitted to the FDA as of October 2024 showed a median DOR of 19 months in the TKI pretreated setting, which compares favorably to our previous median DOR of 17 months from the pooled Trust 1 and Trust 2 results as published in JCO. Perhaps just as importantly, Iptrozi demonstrated meaningful intracranial activity in the second-line setting across both the Trust 1 and Trust 2 studies. This is seen through its confirmed intracranial ORR of 63%, with 15 of 24 patients with CNS metastases who had not received radiation therapy within two months prior to study entry responding to Iptrozi. Intracranial response rate is critically important in ROS1-positive lung cancer since CNS progression has the greatest impact on long-term survival. Having a medicine that has the potential to deliver tumor responses in the brain can make an enormous difference for these patients. Regarding safety, Iptrozi was generally well tolerated and is presented in the label combined across both pivotal Trust 1 and Trust 2 studies. Most adverse reactions were low-grade, transient, and manageable. The most frequently reported adverse reactions, greater than 20%, were diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue. The most frequently reported grade 3 or grade 4 laboratory abnormalities, greater than or equal to 5%, were increased ALT, increased AST, decreased neutrophils, and increased creatine phosphokinase. Regarding CNS reactions due to Iptrozi, and specifically dizziness, the rate was 22%, and more than 90% of this dizziness is grade 1 and transient, lasting about three days. It's also worth noting that our label does not include any warnings or precautions related to CNS effects. Additionally, while diarrhea was the most common GI event due to Iptrozi, the vast majority of this diarrhea was grade 1, occurred in about two days of starting therapy, and was resolved in about one day. Overall, the most common adverse event with Iptrozi is elevation of liver function tests, or LFTs. Our label addresses elevated liver enzymes with monitoring every two weeks during the first two months of treatment, and then monthly thereafter, as clinically indicated, to support patients following therapy. We are very pleased that this liver monitoring is simple and generally follows standard of care practice. Elevation of LFTs is well understood with TKIs, and Oncologists are accustomed to managing these, generally by dose reduction, interruption, or, if necessary, drug discontinuation. To me, the best way to assess tolerability is to observe the rate of drug discontinuation. In our studies, patients infrequently discontinued Iptrozi due to treatment emergent adverse events, or TEAEs. In fact, the overall drug discontinuation rate for Iptrozi due to TEAEs was just 7%, which is low in this space. Finally, in addition to being efficacious and generally well tolerated, Iptrozi is convenient for both patients and prescribers alike, with simple once-daily oral dosing of Iptrozi at 600 milligrams and no need for dose loading or titration. We believe this allows physicians to confidently prescribe Iptrozi and supports long-term use for patients. What does all this mean for Nuvation Bio as a commercial-stage company? We believe the market is primed for new alternatives like Iptrozi, and we've built a commercial infrastructure that's ready to deliver. Our team brings, on average, 15-20 years of deep experience launching therapies in complex, biomarker-driven environments, including at successful oncology companies like Mirati and Seagen. We've assembled 47 oncology account managers supported by regional marketing and field access teams, all focused on removing barriers and accelerating adoption. We know that adoption will hinge on identifying eligible patients, and over the past several months, we've created a blueprint for success for the Iptrozi launch that ensures timely access for patients, strong provider engagement, and operational excellence from day one. We're especially focused on testing, which remains one of the biggest barriers in this space and contributes to widespread underdiagnosis and undertreatment. ROS1 testing rates still lag behind EGFR and ALK, despite inclusion in clinical guidelines, and up to 64% of patients eligible for precision oncology treatments in the U.S. have yet to receive a matched therapy per published data in advanced non-small cell lung cancer. We believe this poor match rate is due to a number of factors beyond inadequate testing, namely the inappropriate use of IO chemo. Our market assessments indicate that currently, a significant number of patients with ROS1-positive lung cancer are receiving IO chemo in the first-line setting. On January 7th of this year, in update from prior guidance, the NCCN now recommends that TKI naive patients with ROS1-positive lung cancer being treated with IO chemo should have that treatment interrupted and be switched to a ROS1 TKI. In fact, IO is now contraindicated in patients with a ROS1 mutation. Furthermore, we believe that the current incidence of ROS1 lung cancer is underestimated by DNA-based NGS testing. We are working to increase awareness and utilization of RNA-based testing, which was introduced last year. We believe RNA-based testing will become the new NGS standard of care, as it is approximately 30% more sensitive in detecting ROS1 fusions than current DNA testing. Our commercial and medical teams understand these issues and are well positioned to resolve them. Now, I'd like to briefly touch on market access, pricing strategy, and patient support. We're excited that Iptrozi is now available to order in the United States through specialty distribution for a competitive gross price of $29,488 per month. This price is below the current gross price of Augtyro and was carefully selected to ensure timely and efficient market access to those in need of Iptrozi. We're actively engaging payers, and we expect coverage policies to align with the label. We're also proud to introduce our patient support program, Nuvation Connect, designed to support appropriate patients throughout their treatment journey and ensure fast, affordable access. The program includes benefits investigation, copay support, dedicated patient services, and reimbursement navigation. To our knowledge, this is the most comprehensive support program available to patients. We are extremely well prepared and excited for this next chapter. We have a differentiated therapy, a different and highly experienced team, and a different go-to-market launch strategy. Most importantly, we remain driven by the patients who have been waiting for a medicine like this, one that offers deep, durable responses, strong CNS activity, and a manageable safety profile. With Iptrozi approved in both the U.S. and China and other global filings underway, we're positioned to expand access to this important medicine and execute with discipline. We continue to do so from a position of financial strength. With this FDA approval, following our first commercial sale, we are poised to receive up to $250 million in non-dilutive financing from Sagard Healthcare Partners, which will further reinforce our already strong balance sheet. Our cash position will easily cover the launch of Iptrozi and the advancement of our broader pipeline and still allow us to achieve profitability without the need to raise additional capital. Furthermore, any excess cash may be used to secure or develop new assets through business development activities, which are currently ongoing. In closing, I'd like to emphasize that every successful launch is about far more than just commercial metrics. It's about patients. Specifically, how many lives can we positively impact? How many patients can now wake up with a little more hope and a little less fear? Here at Team Nuvation, we are humbled and honored to play a role in delivering these benefits to patients. With that, I'll ask the operator to please open the line for questions. Thank you. At this time, we will begin the Q&A answer session. If you'd like to ask a question today, that's STAR followed by 1 on your telephone keypad to enter the queue. Please hold while we compile the Q&A roster. Our first question comes from Kaveri Pellman from Clear Street. Kaveri, your line is open. Please go ahead. Yeah, good morning, and congrats on the approval and favorable label. Thanks for taking my questions. Considering your go-to-market strategy, I just want to understand how will you structure your focus strategy for ROS1 patient community? What volume and classifications of healthcare institutions will rank as your primary targets, factoring in patient population density? What share of the complete available patient market do you foresee capturing via your initial launch and promotional activities? I have a second question. Thanks, Kaveri. We have 47 field reps in the field right now. The majority of patients are still in the community. We have been on the road for months now, just speaking to different healthcare systems and educating people on not only the ROS1 landscape, but also the recent changes in the NCCN guidelines. What's very interesting about the community setting now is that most oncology practices have been consolidated into large healthcare systems, which makes our ability to reach practices much easier given that consolidation. What's also been interesting to us is that over just the last few months, looking since the NCCN guideline changed on January 7th, we've already seen multiple healthcare systems change internal guidelines to reflect the contraindication of IO for ROS1 and the requirement to use a ROS1 agent for ROS1 non-small cell lung cancer. When we look at the current agents that are previously approved in that space and look at our label, we think that our label is clearly the superior label. We believe that our combination of efficacy, especially durability and CNS coverage, combined with our tolerability, makes our drug the clear treatment of choice for this indication. Interestingly, right after ASCO, Nate Purnell from Cleveland Clinic made a comment that he expected taletrectinib to become treatment of choice for the vast majority of patients with ROS1 lung cancer. We certainly agree with that. We've been pleased with the response that we've had from most of these healthcare systems that we've hit, as well as KOLs in the field. Even though this is a relatively rare mutation and type of lung cancer, given the way that the community healthcare has evolved to be consolidated under practices now, instead of waiting for a practice to have a case of ROS1 every one or two years, because these practices now are consolidated in such large healthcare systems, every healthcare system pretty much sees ROS1 every year, which makes it a lot easier to build awareness within the healthcare system and with their own internal guidelines. I think that's really a great tailwind to have. If you look at our—and that also just answers the last part of your question about what share of the market you expect to capture. If you look at the benefits of Xalkori or entrectinib over its competition, and if you look at the benefits of taletrectinib or Iptrozi over its competition, we think that the benefits of taletrectinib are significantly larger over our competition than the Xalkori over its competition. Yet, as you know, entrectinib has virtually 100% market share. We expect to capture the vast majority of this market. We think this is a large market just by—if you just multiply the number of new patients per year by our recently announced price, that's about $1 billion of new patients per year. Given a PFS that so far is already around four years, but maturing, and we believe could extend even significantly farther, that stacking will lead to about $4 billion a year of total potential sales by year four, based on current DNA testing. RNA testing, which is going to become standard of care, will detect about 30% more ROS1 fusions than DNA. So that $4 billion a year market should theoretically increase to about $5.2 billion. We think we should capture far more than 90% of that over time, given just the benefits we have over our competition compared to Xalkori over its competition. We think this is going to be a really big drug, and we're excited that our data have matured in this fashion. We are—and the feedback we've gotten really substantiates and validates that. Got it. All right. That's very helpful. Thank you. And regarding the label, given the two-hour food restriction before and after dosing due to the QT risk, curious about patient and physician comfort with this requirement. Do you anticipate any impact on uptake or adherence? Are there any examples of other drugs where it hasn't been a concern? Thank you. I mean, we have really no concerns at all about this food restriction. I mean, there are four-hour days. Most people don't eat for some four-hour day in their window. This is a QD drug, unlike Repotrectinib, which is a BID drug. Right there, you're already talking about a drug that's far easier to take at some time in a day. There is no dose adjustment with Taletrectinib, unlike Repotrectinib. We don't think that it's going to be any issue at all to find a four-hour window that you can take this drug. Oh, and I'll just add to that that this is how we conducted our clinical trials and there were no issues. Got it. Thank you. The next question comes from Leonid Timashev from RBC Capital Markets. Leo, please go ahead. Yeah. Thanks, guys. Thanks for taking my question. I wanted to ask on the label. I mean, given that you've shown longer PFS and DOR benefits, but those numbers aren't necessarily fully reflected in the label. I mean, can you still detail to that, given that you have publications? And I guess when physicians look at the overall profile, I guess how much of a differentiator was the increased efficacy versus perhaps the tolerability benefits that you guys have? Thanks. Yeah. So I can certainly tell you that by far the most important factor that determines treatment decisions is the durability of responses. I mean, we've always said all along that by far the greatest safety risk to any patient is disease progression. This is a disease that is intrinsically extremely aggressive with a high propensity for brain metastasis. Given the durability of our effects, and especially the CNS coverage, we think that will dwarf any other issues that could be raised. In spite of that, if you look at the tolerability of our drug, at a treatment emergent adverse event rate of 6.5%, that's almost half of Xalkori, which is considered to be an extremely well-tolerated drug. We think that—and the feedback we've gotten from KOLs as well as large healthcare systems is that they expect for our drug to be preferred. I think that that's what we're going to see. We feel really good about that. On top of that, while our JCO publication is already out there, and I've been on the road for the last four months, I can tell you that people that we've spoken to are very familiar with that publication. Everyone was well aware of the 46-month PFS and the combined Trust 1, Trust 2 studies in JCO. Now that median has not been reached, I mean, that's a great thing. I mean, the median is not reached because the drug continues to show incredibly robust durability. As I said, those patients, just in our first 15 patients in phase one, the fact that 20% are still on the drug eight and nine years out. That CR, that patient with a CR at nine years, that patient is going to go on for years more. We do not even know where the median PFS and DOR will ultimately equilibrate, but it is going to be long. We think that already our data set are the most compelling of any drug in the space. We think that that maturity will further emphasize the durability of this drug. We think that's very exciting for patients and for physicians. The next question comes from Soumit Roy from Jones Research. Soumit, your line is open. Please go ahead. Good morning, and congratulations again on the approval. On the approval milestone payment from Sagard, is there any additional color available on the—is there a breakdown of the $250 million or is it a lump sum? The second is the unit price. I do not know if you have disclosed that. It looks like it's coming up to be around $29,000 per month. The third question is, could you elaborate on the DNA versus RNA-based testing on ROS1, why the RNA-based is working better? Is that something you have to develop or a partnership? Thank you for your question, Soumit. To come back to the Sagard deal, remember there are two components to that deal. One is the $150 million royalty financing, and one is $100 million senior term loan. All of these components are eligible as soon as we get commercial sales after approval. The wrinkle in that, and maybe the reason for your question, is that for the $100 million senior term loans, there is one which is available immediately and one that we can use whenever we want in the next 12 months. That is why when we have been talking about it, we have been saying $200 million available initially. That will be the $150 million royalty financing plus the $50 million available immediately. That is $200 million. We have $50 million more of the debt component that we can use whenever we want in the next 12 months. To come back to the royalty financing, which is the bigger part of all of this, $150 million, remember it's 5.5% of U.S. sales below $600 million, 3% above $600 million, and there are caps and everything. We've been saying that if you want to simplify your model, it's about 5% of U.S. sales for $150 million royalty financing, which is like $3 billion if you want in terms of sales. All of this will be available with our first commercial sales, which are obviously imminent. These funds are launched, as we've been saying, and as David has repeated during the call. It provides us with a lot of flexibility on top of our already very robust balance sheet. That's for the financing part. To come back to the price part, which was the second part of your question, yes, we said during the call that the monthly WAC for the drug will be $29,488. $29,488. This amount is the fruit of lots of discussions we have with payers. We had more like 50 payers' engagements in the last six months. Very robust engagement. This is also going to be coming with a very robust support program for patients with reimbursement support, commercial copay, pre-product assistance, bridge program, voucher, etc. All kinds of things to make sure that we are both socially responsible, ensuring that patients in the U.S. can have access to this incredible drug, and also fiscally responsible to the company and our shareholder, and make sure that the launch of Iptrozi will fund the future of the organization as it should. That's the two aspects, and that's why we're at 29,488. Soumit, on your last question about DNA versus RNA, because ROS1 is a gene fusion, RNA finds that a lot easier than DNA. In fact, it's not something that needs to be developed. It's already been developed by multiple companies. Virtually every diagnostics company now has an RNA test. Foundation launched their RNA test in May 2024. It's already been out for more than a year. They expect it to be standard of care within the next year or two. Everyone else has followed. This is not something that we're talking about developing. It's already developed. We do think that's going to increase the incidence of ROS1 diagnosis by about 30%. From about 3,000 new patients per year to about 4,000 new patients per year. That's why we think that if you look at that times our current drug price, that should be about, and with the revenue stacking just based on about four-year PFS, that should be about $5.2 billion per year by year four. Great. Thank you so much again, and congrats. Thank you. The next question comes from Yaron Werber from TD Cowen. Yaron, your line is open. Please go ahead. All right. Thanks so much and congrats. Nice to really see this and even ahead of schedule. Got a couple of questions. Number one, do you have a sense how many patients are currently getting treated in the U.S.? I mean, Xalkori probably has the largest share, right, followed by Rozlytrek. I don't know if you have a little bit of a sense there. And then I have a quick follow-up as well. We just look at current sales of the current TKI times their drug price and divide by drug price. The number of patients on a TKI seems to be somewhere between 1,000 and about 1,500. Recall that the durability of the first-time TKIs is significantly shorter. They're coming off therapy fairly quickly because, as you know, entrectinib's PFS is about 16 months. That's one example. On top of that, we know that if you look at the IQVIA data for repotrectinib, about 10% of scripts are being discontinued every month. About 50% drop off by five months, primarily because of the CNS tolerability. That number we think will be very different for a drug that has a much longer PFS. I mean, at 46 months, that's almost triple the entrectinib PFS. We believe that without even any CNS warnings in our label, that's the main reason for discontinuation of the only second-generation TKI. We think that we will address that readily. We think that that will lead to time on a drug that just hasn't been seen to date with any ROS1 TKI. As you know, a prevalent story is far more important than an incident story for revenue generation. We think that we're set up for that. The other point to add to that, Yaron, is that—I'm sorry, just once again—is that everything that David had said about the NCCN guideline and the change, we've already seen the number of scripts for ROS1 TKI increase about 20% since those change, which is a very significant trend and shows everything that we've been saying about NCCN guideline being translated in practice, and which is the right thing for patients. That drives the market up, obviously, because this is the right thing to do. Yeah. You also have really good activity in the most common mutation, the G2032R, in general in second line. Any sense, what percentage of patients develop that mutation? I'm thinking about when patients fail the current drugs and then switch. Yeah. So G2032R develops in over 40% of patients. So it's a significant resistance mutation. What is interesting is that if you look at the G2032R response rate, while Iptrozi appears to be at the top of the response rate of all the ROS1s, it is not dramatically different from repotrectinib, which is a very effective drug. If you look at their published resistance G2032R response rate, it is still 59%, which is pretty close to where we are. What is interesting then is that no one has mapped out all the resistance mutations for ROS1. While G2032R is the most common, there are probably a lot of other things that go into patients progressing. We did not have it mapped out, all those mutations. That is why PFS is by far the best metric about how good you are at preventing resistance. We would say that given our 46-month PFS, while we haven't mapped out all the possible resistance pathways, clearly Iptrozi is doing something right in that regard. We think that G2032R is only a small facet of the multiple potential pathways for development of resistance. Our PFS speaks to Iptrozi being best in class in that regard. Maybe just last question. You mentioned you've been enrolling more patients in TRUST 2. Are you done enrolling at this point? What was the reason for that? Would you then submit that data to FDA? Thank you. Oh, yeah. Hi, this is Kerry. I'll take that question. We are going to stop enrolling any further in the TRUST 2 cohorts that we currently have open. The reason why we did continue to enroll is that we needed to provide additional data to the agency during the review with respect to dose optimization. If you'll recall, we had cohort 5, and that's where we randomized patients to 400 and 600 milligrams q.d. and provided that data during the review. Obviously, in their assessment, they support 600 milligrams as the appropriate dose. That was the reason for continuing enrollment, but that will now close. Yaron, I want to raise one other anecdote regarding your question about resistance. Because drugs can either do something or they can't. If they can, then obviously that can be done again and again. We had a very interesting recent case because, as you know, Trust 1 was performed in China, conducted in China, where repotrectinib was not available at the time. We did not have repotrectinib experience in China. We were informed recently, just a month ago, of an MD Anderson patient who was 38 years old, diagnosed with ROS1, really aggressive disease, completely progressed on IO chemo, failed that, went on to entrectinib, failed that, got put on repotrectinib, and on repotrectinib developed 23 brain mets. Clearly did not respond to that. Was actually going to hospice, but got into cohort 5 of the TRUST 2 study, has an incredible response. Is now eight months out and feels like a normal person. It was not people walking into his visit on repotrectinib. It is now walking into the clinic and conducting a normal life. We just think that while that is only an anecdote, drugs can either do something or they cannot. That patient is a different person on taletrectinib. That is why we think that this drug, that is an example of the kind of response we are getting that we think contributes to an unprecedented PFS and DOR that you have seen in the JCO publication. The next question comes from Sylvan Terkin from Citizens. Sylvan, your line is open. Please go ahead. Yeah. Good morning and congratulations on this great update. Maybe a more general question about how exactly you are instructing the sales force, or what your strategy here is in how to improve testing rates and also the action rates. You just alluded that the NCCN guidelines already led a 20% increase in scripts. How can you further push that up? And how much more room is that on the action, on the mutation rate there? I have a quick follow-up on how many lives covered or how many formularies you are on and what you expect the governmental versus commercial coverage split to be here depending on the age. Thank you. Yeah. On testing rates, it differs between academic centers and the community. In academic centers, testing rates are nearly 100%. In the community, we think it's about half of that. That's changing significantly because, as you know, since the advent of precision oncology lung drugs for EGFR, ALK, RET, and now ROS1, it is literally medical malpractice not to test for precision oncology mutations for which there are drugs that are still effective. Interestingly, if you just look at, I was at the Ochsner Cancer Center in Louisiana, and Louisiana became the first state to pass state legislation that now requires NGS testing if you have lung cancer. I think that's a great development, and I think that hopefully all states will follow that. I think it's becoming increasingly recognized, especially for lung cancer, for a disease that used to be considered untreatable. Lung cancer has now become one of the most treatable cancers on the planet, especially with EGFR, ALK, RET, and now ROS1. I think that testing rates are going to increase significantly. In the multiple health systems I visited over the last four months, we're seeing huge initiatives within those systems to increase physician awareness, speaking about what to do about it with the NCCN guidelines and to mandate ROS1 therapy for ROS1 patients. I do think that's going to change significantly. Do you want to talk? Yeah. As we've been saying, the typical ROS1 NSCLC patient is younger than average, about 50 years old, which means that the share of commercial patients will be much higher than in other lung cancer. We expect more than half of patients to be commercial patients, and then probably about 40% Medicare, some Medicaid, and some VA/DOD. More than half will be commercial patients. Great. Thank you. Maybe a quick follow-up here. Is there any timeline to when the label may be updated specifically to include eventually TRUST 2 duration of response data? Thank you. Yeah. I'll take that question. There are going to be kind of two analyses that are ahead of us, and we're working on the modeling right now. One would be an update to the pretreated population for TRUST 2, which we would anticipate hopefully sometime by the end of this year. Then the others in the TKI naive population. To David's point, we need events in order to reach the median, and that means patients need to progress. Their duration of response has just been remarkably long. It is difficult for us to have a handle on that right now. As we get more events, we continue to follow the patients, and we will have a better sense. At least for the pretreated, we do think that we hopefully will have a label update into the agency by the end of this year. Great. Thank you so much. Congrats again on this great milestone. Thank you. The next question comes from Michael Yee at Jefferies. Michael, your line is open. Please go ahead. Hey, good morning. Thanks for your questions. Congrats on the approval. Fantastic. David, two questions. One was just thinking about the first year of the launch. I know there will be focus on sales and the success metrics of the launch. Do you expect that this is primarily a blocking and tackling going out there and getting to all these sites and trying to get all of these first-line patients with ROS1? Or do you think that there will also be people who are swapping and coming off of TKIs? Just sort of give us a picture of how you think and which types of patients will be coming on in the first year given ROS1 testing. The second question is maybe a bit of housekeeping, but is this a full approval? I noticed with Repo, it's designated technically as accelerated approval, but yours actually seems pretty broad and doesn't necessarily mention any of that. I just want to confirm any additional requirements because it does seem quite positive around your approval and indication versus competitors. Thank you. Great. I'll start with the second question first. It is a full approval. There's nothing else we need to do. We're done. On your first question, I think that all launches involve a lot of blocking and tackling, no matter what. As good as any drug is, I think it's always a lot of blocking and tackling. With regard to swapping, the standard practice in oncology has been you do not swap a patient out until they progress. We think that there are actually reasons to swap at least some TKIs for Iptrozi off the bat, which is if you look at this particular disease where 36% of people who get diagnosed are diagnosed with a brain metastasis, and the fact that 50% of people, when they do progress, will progress with the brain as the first site of disease progression, this is a disease you need to have CNS coverage. Giving a drug that does not have CNS coverage is just not great medical practice. We think that given the fact that Crizotinib, which is the most widely used TKI, does not cross the blood-brain barrier, it would be inappropriate for physicians to continue Crizotinib when Iptrozi is available. We have been speaking to multiple practices and healthcare systems about this. While I don't know if it's easy to get oncologists to change their practice, in general, it isn't easy. We do think there's, in this particular case, a really strong rationale why they should switch. We do know, though, that in spite of what practices Pavan's there are, entrectinib or crizotinib, the PFS is only about a year and a half. They're going to be coming off therapy in relatively short order. We know from repotrectinib that their discontinuation rate, especially due to CNS effects, is substantial, 10% a month. Those patients will certainly be switched to a more tolerable agent. We do expect Iptrozi to be used in switches in those kinds of cases. We do think that it's important by the change practice to make sure that CNS coverage with a really robust, durable drug is given right as early as possible, which we think is immediately upon diagnosis. That's what we're going to be pushing for. Whether or not how long it takes to change physician practice always takes some time. In this particular case, we think the rationale is so clear, we hope that it's accelerated a bit beyond standard switching practices. Very good. Thank you. There are currently no other questions queued at this time, so I'll turn it back over for closing remarks. We want to just thank all of you for your support. We're super excited about this launch. We think this is going to be one of the great drugs in oncology. We're so delighted to be able to offer patients with such a devastating disease this kind of durability of response and this kind of tolerability profile. We'll keep you updated on new developments that occur. We hope to do another data cut sometime later this year. If we happen to hit a meeting at that point, we'll certainly be updating the label. Again, what we're saying, we have no idea how long this can go on for. We think this drug is showing durability that even we did not expect. All a high-class problem, but we'll keep you updated as we get more data. Thank you so much. This concludes today's conference call. Thank you for your participation. You may now disconnect your lines.