Nuvation Bio Inc. (NUVB) June 2025 Conference Transcript

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 talotrexanib, now known under the branded name Ibtrozi in the United States. Ibtrozi 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 novationbio.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 ECTROZI, 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 Hong. David?

Thanks, JR, and thank you all for joining us today. This is a truly exciting moment for Novation 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 Iptrosi, Novation 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. And 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, Iptrosi had been granted breakthrough therapy designations by the FDA in both the first and second-line settings. No other drugs currently in development have this designation. DIPTROZI accordingly received priority review for its NDA submission, but we are so pleased to receive approval weeks prior to our PDUPA date of June 23. And finally, I would like to thank the dedicated team at Novation Bio for their relentless focus, persistent passion, and unwavering commitment that resulted in today's announcement. At our core, Division 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, Rothland-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. And despite having targetable mutations, they unfortunately face a high risk of disease progression. To address this unmet need, we developed EFTROZI, a next generation highly selective ROS1 TKI, now approved for the treatment of adults with locally advanced or metastatic or often positive non-small cell lung cancer. It truly 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 ATROSI 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. And this database continues to grow. Since NDA submission, we have enrolled additional patients in the Global TRUST2 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, the TROSI 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 posted 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 the frozen 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 Etrosia 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 didn't 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 teletrackinib in our previously mentioned JCO publication. That dataset was based on a data cutoff date of June 2024, nearly one year ago. Our labelled discussions with FDA were based on a more recent data cutoff of October 2024 for 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, Iptrosy's very first clinical trials were initiated a little over nine years ago. As an example of what Iptrosy's durability of responses have meant for TKI-naive patients, in a recent follow-up of the 15 patients dose in one of the earliest ever studies for Iptrosy, a phase one study in TKI-naive settings, 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 the trozos. 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 non-small cell lung cancer are still continuing to receive Ibtrozi, approaching a decade from treatment initiation. It's 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 Ibtrozi might further extend in this setting. Robust results were also observed in patients previously treated with a ROS1 TKI, also known as the TKI pre-treated population. In TRUST 1, TKI pre-treated patients who received iptrose achieved a confirmed ORR of 52% and had a median DOR of 13 months with median follow-up of 33 months. And in TRUST 2, our predominantly Western study, TKI pre-treated patients treated with iptrose achieved particularly impressive results including a confirmed ORR of 62 percent. While not included in the label given the shorter follow-up time, the TRUST2 data submitted to the FDA as of October 2024 showed a median DOR of 19 months in the TKI pre-treated 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. And perhaps just as importantly, Iptrosi 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 metastase who had not received radiation therapy within two months prior to study entry, responding to Iptrosia. Intracranial response rate is critically important in ROS1-positive lung cancer, since CNS progression has the greatest impact on long-term survival. So having a medicine that has the potential to deliver tumor responses in the brain can make an enormous difference for these patients. Regarding safety, Iptrosia 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, fizziness, 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 ASP, decreased neutrophils, and increased creatine phosphatidinase. Regarding CNS reaction theory of chozy, and specifically busyness, the rate was 22%, and more than 90% of this busyness is grade one and transient, lasting about three days. It is also worth noting that our label does not include any warnings or precautions related to TNS effects. Additionally, while diarrhea was the most common GI event due to Iptrosi, the vast majority of this diarrhea was grade one, occurred in about two days of starting therapy, and was resolved in about one day. Overall, the most common adverse event with Iptrosi is elevation of liver function tests, or LFTs, and 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. And in our studies, patients infrequently discontinued and chosen due to treatment-emergent adverse events, or TEAEs. In fact, the overall drug discontinuation rate for eptrosi due to TEAEs was just 7%, which is low in this space. Finally, in addition to being efficacious and generally well tolerated, eptrosi is convenient for both patients and prescribers alike, with simple, once-daily oral dosing of eptrosi at 600 milligrams, and no need for dose loading or titration. We believe this allows physicians to confidently prescribe Iptrosi and supports long-term use for patients. So what does all this mean for NuVision Bio as a commercial stage company? We believe the market is prying for new alternatives like Iptrosi, and we've built a commercial infrastructure that's ready to deliver. Our team brings, on average, 15 to 20 years of deep experience launching therapies in complex, biomarker-driven environments, including at successful oncology companies like Medivation, Mirati, and CGen. 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 change in identifying eligible patients, and over the past several months, we've created a blueprint for success for the Affiliate 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 under-diagnosis and under-treatment. ROS1 testing rates still lag behind EGFR and ALK, despite inclusion in clinical guidelines, and up to 64% of patients eligible for precision oncology treatment in the U.S. have yet to receive a match therapy for 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 IL chemo. Our market assessments indicate that currently a significant number of patients with Ross 1-positive lung cancer are receiving IL chemo in the first-line setting. On January 7th of this year, an 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. And in fact, IO is now contraindicated in patients with a ROS1 mutation. Furthermore, we believe that the current incidence of raw cell 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 percent more sensitive in detecting raw cell infusions 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 it's TROSI 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 Octiro and was carefully selected to ensure timely and efficient market access to those in need of iftrosy. 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, Novation Connect, designed to support appropriate patients throughout their treatment journey and ensure fast, affordable access. The program includes benefits, investigation, co-pay 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. But 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 the trilogy 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. And 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 CIGAR healthcare partners, which will further reinforce our already strong balance sheet. Our cash position will easily cover the launch of Iptrosi 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 patience. 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 one on your telephone keypad to enter the queue. Please hold while we compile the Q&A roster. Our first question comes from Kaviri Pullman from Clear Street. Kaviri, your line is open. Please go ahead.

Yeah, good morning, and congrats on the approval and favorable label, and thanks for taking my questions. Considering your go-to market strategy, I just want to understand how will you structure your focus strategy for ROST1 patient community? what volume and classifications of healthcare institution will rank as your primary target, factoring in patient population density, and what share of the complete available patient market do you foresee capturing via your initial launch and promotional activities? And I have a second question.

Thanks, Kaveri. So, you know, we have 47 field reps in the field right now. The majority of patients are still in the community, so 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 is change internal guidelines to reflect the contraindication of IO for ROS1 and the requirement to use a ROS1 agent for small cell lung cancer. 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, and 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, ASCO, Nate Purnell from Cleveland Clinic made a comment that he expected teletrackin to become treatment of choice for the vast majority of patients with ROS1 lung cancer, and we certainly agree with that. But we've been pleased with the response that we've had from most of these healthcare systems that we've hit, and as well as KOL from the field. And 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 great tailwinds they have we you know if you look at our um to answer and then also just answer the last part of your question about what share of the market you expect to capture if you look at um the benefits of um the gristle or somertinib over its competition and if you look at the benefits of teletrack that we have trozi over its competition. We think that the benefits of teletretnib are significantly larger over our competition than the gristle over its competition. And yet, as you know, Osimertnib has virtually 100% market share. So we expect the cash 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 a billion dollars of new patients per year. But 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 ROS-lung fusion 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 Bristol and its competition. So we think this is going to be that our data have matured in this fashion, and the feedback we've gotten really substantiates and validates that.

Got it. That's very helpful. Thank you. And, you know, 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, and 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 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 Reprotreptin, which is a BID drug. So, right there, you're already talking about, you know, a drug that's far easier to take at some time in a day. There is no dose adjustment with Palotreptin, unlike Reprotreptin. So we don't think that it's going to be any issue at all to find a four-hour window.

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.

Next question comes from Leo Timoshev from RBC Capital Market. Leo, please go ahead.

Yeah, thanks, guys. Thanks for taking my question. I wanted to ask on the label. I mean, given that, you know, you've shown longer PFS and DOR benefits, but that's not necessarily, 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, you know, the tolerability benefits that you guys have?

Yes, I can certainly tell you that by far the most important factor that determines treatment decisions is the durability of responses. I mean, you know, we've always said all along that, you know, 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. And 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, you know, at a treatment emergent-related adverse event rate of 6.5%, that's almost half of chrysanthemum, which is considered to be an extremely well-tolerated drug. so we think that you know and the feedback we've gotten from kols as well as large healthcare systems is that they expect for our drug to be preferred and i think that that's what we're that's what we're going to see uh so we feel really good about that on top of that um you know while um our jco publication is already out there uh and i've been on the road for the last four months and i can tell you that people that we've spoken to are very familiar with that publication everyone was well well aware of the 46-month pfs and the combined trust-wide justice studies and jco but now that meeting has not been reached i mean that's a great thing i mean the meeting is not reached because the drug continues to show incredibly robust durability and as i said you You know, 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, and that CR, that patient with a CR at nine years, that patient's going to go on for years more. So we don't even know where the median PFS and DOR will ultimately equilibrate, but it's going to be long. And we think that already our data set are the most compelling of any drug in the space. And we think that that maturity will further emphasize the durability of this drug. And we think that's very exciting for patients.

The next question comes from Sumit Roy from Jones Research. Sumit, your line is open. Please go ahead.

Good morning, and congratulations again on the approval. On the approval milestone payment from Sager, is there any additional color available on the – is there a breakdown of the $250 million as a lump sum? And second is the unit price. I don't know if you have disclosed that. It looks like it's coming up to be around $29,000 per month. And the third question is, could you elaborate on the DNA versus RNA-based testing on ROS1, why the RNA-based is working better, and is that something you have to develop or the partnership?

Thank you for your question, Summit. So to come back to the SAGA deal, remember there are two components to that deal. One is the $150 million royalty financing, and one is $100 million senior term loan. so all of these components are eligible as soon as we get commercial sales after approval so but the wrinkle in that and maybe the reason for your question is that for the 100 million senior term load there is one which is available immediately and one that we can use whenever we want in the next 12 months so that's why when we've been talking about it we've been saying 200 million available initially that will be the 150 million royalty financing plus the 50 million available immediately that's 200 million and then we have 50 more of the debt components that we can use whenever we want in the next 12 months to come back to the royalty financing which is a bigger part of all of this 150 million remember it's 5.5 percent of us sales below 600 million three percent above 600 million and there are cats and everything so we've been saying that you know if you want to simplify your model, it's about 5% of US sales for $150 million royalty financing, which is like $3 billion if you want in terms of sales. So all of this will be available with our first commercial sales, which are obviously imminent. And these funds are launched, as we've been saying and as David has repeated during the call, and it provides us with a lot of flexibility on top of already very robust balance sheet. So 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 work for the drug will be 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, so very robust engagement. This is also going to be coming with a very robust support program for patients with reimbursement support, commercial co-pay, free product assistance, bridge program, voucher, et cetera, et cetera, all kind 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 Itrosi will found the future of the organization as it shoots. Well, that's the two aspects, and that's why we have 29,488.

And, Sumit, your last question about DNA versus RNA. Because ROS1 is a gene fusion, RNA finds that a lot easier than DNA. And, in fact, it's not something that needs to be developed. It's already been developed, and by multiple companies. So, virtually every diagnostics company now has an RNA test. Foundation launched their RNA test in May of 2024. So it's already been out for more than a year. They expect it to be standard of care within the next year or two. And everyone else is followed. So this is not something that we're talking about developing. It's already developed. And we do think that's going to increase the incidence of loss from diagnosis by about 30%. So from about 3,000 new patients per year to about 4,000, and that's why we think that if you look at that times our current 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.

Thank you so much again, and congrats.

The next question comes from Jaren Verber from TD Cameron. When Yaron, your line is open, please go ahead.

Great, 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, chrysotinib probably has the largest share, right, followed by Roslatrex. I don't know if you have a little bit of a sense there, and then I have a quick follow-up as well.

So, if you just look at current sales of the current TKIs times their drug price and divided by drug price, the number of patients on a TKI seems to be somewhere between 1,000 and about 1,500. But recall that the durability of the first 10 TKIs is significantly shorter, so they're coming off therapy fairly quickly because, as you know, intractinibs, 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. So about 50% drop out by five months, primarily because of the CNS tolerability. So that number, we think, will be very different for a drug that has a much longer PFS. I mean, at 46 months, it's almost triple the intracted in PFS, and we believe that, you know, without even any CNS warnings in our label, that's the main reason for this continuation of TKI. We think that we will address that readily, and we think that that will lead to, you know, time on drugs that have any wrong.

The other point to add to that, Garen, is that, I'm sorry, just once again, is that everything that David has said about the NCCN guideline and the change, We've already seen the number of scripts for ROS1 TKI increase about 20% in those changes, which is a very significant trend and shows everything that we've been saying about NCCN guidelines being translated in practice, which is the right thing for patients, and that drives the market up, so this is the right thing to do.

Yeah, you also have really good activity in the most common mutation, the G2032R in general and second-line, in any sense, what percentage of patients develop that mutation? I'm thinking about when patients have been on the current drugs and then switch.

Yeah, so G2032R develops in over 40% of patients. So it's a significant resistance mutation. But what's interesting is that if you look at the G2032R response rate, while diptrozzy appears to be at the top of the response rate of all the ROS1s. It's not dramatically different from ripotrechnite, which is a very effective drug. If you look at their published resistance G232R response rate, it's still 59%, which is pretty close to where we are. So what's interesting then is that no one has mapped out all the resistance mutations for ROS1. And while G232R is the most common, there are probably a lot of other things that go into patients progressing. And we haven't mapped out all those mutations. So that's 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, Epitrozy is doing something right in that regard. And so we think that GD2032R is only, you know, a small facet of the multiple potential pathways for development of resistance. But our PFS speaks to Eptrosis being best in class in that regard.

And maybe just last question. So you mentioned you've been enrolling more patients in Entrust 2. Are you done enrolling at this point? And what was the reason for that? Would you then submit that data to FDA?

Hi, this is Carrie. I'll take that question. So, we are going to stop enrolling any further in the TRUST2 cohorts that we currently have And 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 five, and that's where we randomized patients to 400 and 600 milligrams QD and provided that data during the review. And obviously, in their assessment, they support 600 milligrams as the appropriate dose. So that was the reason for continuing enrollment, but that will now close.

And I want to raise one other anecdote regarding your question about resistance, because drugs can either do something or they can't, and 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 their reproductive was not available at the time, so we did not have reproductive experience in China. we were informed recently just a month ago of an md anderson patient who had 38 years old diagnosed with ross one really aggressive disease completely progressed on io chemo failed that went on to intractinib failed that got put on reprotractinib and on reprotractinib developed 23 brain meds so clearly did not respond to that i was actually going to hospice that got into cohort five of the trust to study and a incredible response is now eight months out and feels like a normal person. It wasn't people walking into this visit on reproductive is now walking into the clinic and conducting a normal life. So we just think that while that's only an anecdote, drugs can either do something or they can't. And that patient is a different person on teletretanib. And that's why we think that this drug, that's an example of the kind of response we're getting that we think contribute to an unprecedented PFS and DOR that you've seen in the JCO publication.

Question comes from Sylvan Turkin from Citizens. Sylvan, your line is open. Please go ahead.

Yeah, good morning and congratulations on this great update. I just maybe a more general question about how exactly you're instructing the Salesforce 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 percent 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? And then I have a quick follow-up on how many lives covered or how many formulas you're on and what you expect the governmental versus commercial coverage split to be here, depending on the age.

Yeah, so 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. But that's changing significantly because, as you know, since the advent of precision oncology lung drugs for EGFR, ALK, RAT, and now ROS1, it is literally medical malpractice not to test for precision oncology mutations for which there are drugs that are so effective. And interestingly, if you just look at, I was at the Oxford Cancer Center in Louisiana, and Louisiana became the first state to have to pass state legislation that now requires NGS testing if you have lung cancer. And I think that's a great development, and I think that hopefully all states will follow that. But 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, ALP, RET, and now ROS1. So I think that testing rates are going to increase significantly. And in the multiple health systems I've 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. So I do think that's going to change.

Yeah, so as we've been saying, the typical WAS-1 and a CLT patient is younger than average, about 50 years old, which means that the share of commercial patients would be much higher than in ulcer lung cancer, so we expect more than half of patients to be commercial patients, and then probably about 40% Medicare, some Medicaid, and some VADOD, but about more than half will be commercial patients.

Great, thank you. And maybe a quick follow-up here. Is there any timeline to when the label may be updated specifically to include, you know, eventually Trust-2 duration of response data? Thank you.

Yeah, I'll take that question. So, there are going to be kind of two analyses that are ahead of us, and we're working on the kind of the modeling right now. Now, one would be an update to the pretreated population for TRUST2, which we would anticipate hopefully sometime by the end of this year, and then the others in the TK-naive population. And to David's point, we need events in order to reach the median, and that means patients need to progress. And their duration of response has just been remarkably long. So it's difficult for us to have a handle on that right now. But as we get more events, we continue to follow the patients. We'll have a better sense. But at least for the pretreated, we do think that we'll hopefully will have a label update into the agency by the end of this year.

Thank you so much. And congrats again on this great milestone. Thank you.

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. And the second question is maybe a bit of a 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. So I just want to confirm any additional requirements because it does seem quite positive around your approval and indication versus competitors.

Great. so i'll start with the second question first um it is a full approval so um there's nothing else we need to do we're done on the on your first question i think that all launches involve a lot of blocking and tackling no matter what you know no matter what as good as any drug is i think it's always a lot of blocking and tackling but uh with regard to swapping you know the standard practice oncology has been you don't swap a patient out until they progress um but we think that there are actually reasons to swap at least some TKIs for Eptrozzi off the bat which is if you look at this particular disease where 36 percent of people who get diagnosed are diagnosed with a brain metastasis and the fact that 50 percent of people when they do progress will present progress with the brain as the first site of disease progression this is a disease you need to have CNS coverage and giving a drug that doesn't have CNS coverage is just not great medical practice. So we think that, given the fact that chryzotamib, which is the most widely used TKI, doesn't cross the blood-brain barrier, we think it would be inappropriate for physicians to continue chryzotamib when Ibtrozi is available. And so we've been speaking to multiple practices and healthcare systems about this. And, well, 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 practice patterns there are, intracnib or chrysotinib only, the PFS is only about a year and a half. So they're going to be coming off therapy relatively short order. And we know from repotractive that their discontinuation rate, especially due to CNS effects, is substantial, 10% a month. So those patients will certainly be switched to a more tolerable agent. So we do expect, if chosen, to be used in switches in those kinds of cases. But we do think that it's important to try to change practice to make sure that CMS coverage with a really robust, durable drug is given right as early as possible, which we think is immediately upon diagnosis. So that's what we're going to be pushing for. But whether or not, you know, how long it takes to change physician practice, it always takes some time. But in this particular case, we think the rationale is so clear. and we hope that it's accelerated a bit beyond standard, you know, switching practices.

There are currently no other questions to you at this time, so I'll turn it back over for closing remarks.

Well, 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. So we'll keep you updated as new developments occur. We hope to do another data cut sometime later this year. And if we have the intermediate at that point, it'll certainly be updating the label. But, you know, given what we're seeing, we have no idea how long this can go on for it. We think this drug is showing durability that even we did not expect. So all a high-class problem, but we'll keep you updated as we get more data. So thank you so much.