Welcome to Tyra Biosciences webcast and conference call on the initial SURF302 results. Today's conference is being recorded. At this time, I would like to turn the call over to Todd Harris. Please go ahead. Thank you, Operator, and good morning, everyone, and thank you for joining us. I'm Todd Harris, CEO at Tyra Biosciences, and we are thrilled to be sharing with you the results that we're seeing in our SURF302 study evaluating oral dabogratinib in patients with intermediate-risk NMIBC. I'd like to begin by thanking the patients, their families who participated in this study, our investigators, study coordinators, employees, and our shareholders. None of this would be possible without you. Before we begin, I'd like to remind everyone that during today's presentation, we will be making forward-looking statements, including statements about our future clinical plans, data and strategy, and potential therapeutic benefits of dabogratinib. These statements are subject to risks and uncertainties that could cause actual results to differ material. Please refer to the slide and our SEC filings for cautionary language and a discussion of these risks. We undertake no obligation to update these forward-looking statements except as required by law. I'm pleased to be joined by our Chief Medical Officer, Doug Warner, also Dr. Mark Silva from Greater Boston Urology, a community urologist out of Boston who's actually participated in both of our SURF302 and SURF303 studies. He's here to share his perspective on both the data and the impact of oral dabogratinib for his potential patients and practice. I'll share some market insights up front. Doug's going to be walking through the data, and we have other members of our team, including Alan as well. We are excited to share today that we believe we have a drug with dabogratinib. At the 60 mg dose, we are seeing the safety for chronic dosing, the clinical efficacy, and the convenience of an oral therapy that could truly shift the paradigm of treatment in this setting of intermediate-risk NMIBC. I've talked a lot about the patient journey in the past. Patients with intermediate-risk NMIBC suffer from multiple procedures, surgeries, and over-instrumentation. It is the key unmet need. For the first time with the data we're sharing today, we can envision a future where the procedural burden could be replaced with the convenience of a simple oral drug at home. This population, of which there are about 50,000 new patients seeking treatment every year, 70% of these patients actually opt out or forego an effective treatment that's been proven to reduce recurrence. That's a treatment involving induction and maintenance chemo, and it's in the guidelines. Why are they opting out of or foregoing this effective treatment? It is because this is a disease that is not likely to progress, but is highly recurrent, and facing the choice between multiple catheterizations and procedures that would be required to maintain a disease-free status, most patients are simply waiting to recur, and when they do recur, undergoing a single operative procedure instead of the multiple catheterizations. When we look specifically at the largest population, the FGFR3-positive population, it is clear this is the population with the highest unmet need. Really meaningful data from Dr. Meeks at AUA this year highlighted that FGFR3-positive patients have a median recurrence-free survival of only 16 months, versus the broader population that is not FGFR3 having a median RFS of 40 months. It is clear that this is a signal that is causing multiple and frequent recurrences, and by suppressing this signal, we have the opportunity to change the patient journey, bend the curve towards a longer disease-free survival. The evidence is already there. We have seen with intravesical and oral pan-FGFR inhibition that as long as FGFR3 is being suppressed, we can see 100% durability. But in all of these examples, when that FGFR3 suppression signal goes away, patients come off treatment, we see a high rate of recurrence that starts to happen right away. Three of four evaluated patients in that TAR-210 phase II study actually came off of therapy and recurred within three months. Four of six patients who had discontinued treatment have recurred within a year. When we think about how can we maintain treatment and the broader pipeline, all of the approaches that are moving into phase III adjuvant studies require multiple urethral violations to be effective. This is continuing this paradigm where patients today are voting with their feet not to undergo treatment. With an oral drug in dabogratinib, we have the potential for chronic suppression, chronic dosing with the safety signal and the efficacy signal we are talking about today, that it could actually change the paradigm for these patients in maintaining a response and avoiding recurrence. The study that we designed to demonstrate this is our SURF302 study, and it is the data we will be sharing today. It is important to highlight that this is a marker lesion study. What does that mean? That means that at least one marker was left behind in the tumor and drug was given to identify which dose can we see that marker lesion shrink or disappear. We actually, with the design of this study, have two studies in one. We allowed both patients with a single marker lesion, which is a really high predictor of adjuvant success, and this was the criteria that the one predecessor study, THOR-2, the criteria that they used. But we also looked at patients with multiple marker lesions, which could give an initial indication of dabogratinib's use in an ablative setting. We tested two doses, 50 and 60 mg. Both of these doses were chosen as potential doses to cover our IC50, which has an AUC of 2,500 ng times hour per mil. We will highlight in the data today why that is important and why we think that we are seeing a great dose response between 50 and 60 mg. Finally, the endpoints. The primary endpoint was CR at three months. Because of the importance of the adjuvant signal when a lesion is shrinking greater than 50% and no new lesions are appearing, we also look at best overall response as a clear indicator that there is enough drug on board with a particular dose to shrink the tumor and to potentially have an effect in an adjuvant setting. What are we seeing? Initial data shows that when we look at the study with single marker lesions, we have 100% ORR at our 60 mg dose. Recall, this is an ablative signal-seeking study, so when we look at these single-marker lesions, and this was the way that the THOR-2 study was ran, we see 100% ORR, and we see a best overall response of 75% CR. This is exactly the benchmark we were hoping to see. THOR-2-like efficacy, but with a much-improved tolerability, which, as Doug walks through the data today, you will see. At 60 mg, we are seeing the safety signals that could support chronic dosing potential. All this comes together to highlight a very high probability of success in an adjuvant phase III. So 60 mg is the go-forward dose we are planning for an adjuvant phase III versus a placebo. What the data also show here, and we will highlight this, that with multiple marker lesions, the responses are not as strong. When we think about the potential of using dabogratinib in an ablative setting, it is clear that potential more drug on board could be helpful for ablation, so we will be studying a 70 mg dose expansion in SURF302 prior to considering whether we further expand this study towards lesions of all sizes in an ablative setting. To be clear, the biggest opportunity we are pursuing, where 85% of the market, we believe is in the adjuvant setting, and that is the phase III dose selection that we are moving forward with and talking about today at 60 mg. With that, let me hand it over to Doug to get into the study details. Doug? Thank you, Todd. SURF302 enrolled a highly recurrent untreated population. This is very consistent with the overall patient population in low-grade IR-NMIBC. This is an elderly group of patients, the vast majority of which had recurrent disease and had prior TURBTs up to 10. Interestingly enough, as Todd pointed out, this patient population, the majority did not receive intravesical chemotherapy. This patient population had a high tumor burden, with over a third of patients had greater than one marker lesion at baseline. In addition, total aggregate tumor size was 10 mm in a quarter of the patients. Overall, when we look at the safety data, dabogratinib showed favorable safety and tolerability that support chronic dosing in this indication. Adverse events were manageable. There was no clinically significant hyperphosphatemia, nail toxicity, or ocular toxicity. These are common toxicities that affect quality of life that are associated with pan-FGFR inhibitors. Importantly as well, there's a low frequency of transaminase increases. When we look at dose modifications, first at the 60 mg dose, there were no dose discontinuations or reductions. There were only two AE-related dose interruptions that were related to dabogratinib. At the 50 mg dose, we had one dose discontinuation and one dose interruption, and I'll go into those two cases in a little more detail in a second here. We look at the overall safety data. The vast majority of treatment emergent adverse events were mild and moderate, so low-grade. At the 60 mg dose, we had three Grade three UTIs. These were all unrelated events. At the 50 mg dose, we had two Grade three events. One of these events was a Grade 3 rash, which resolved with dose interruption and low-dose steroids. The other Grade three event occurred in a patient who had normal LFTs and then was started on Macrobid for a UTI, a known liver-toxic drug, and subsequently developed Grade three AST/ALT elevation and was discontinued from study drug. Looking at the treatment-emergent adverse events of greater than 10%, the level of fatigue is consistent with what is seen in the placebo arm of trials in this patient population. We have not seen a fatigue signal in the data to date with dabogratinib. Dry eye, there were Grade one dry eye events. Grade one dry eye is an asymptomatic event, so the question is: how did we pick up these events? It's because since pan-FGFR inhibitors are associated with ocular toxicity, regulators asked us to perform comprehensive eye exams regularly, so we had these exams every three months, and these were asymptomatic findings that were picked up on these exams. I want to go into a little more detail on the episodes of diarrhea in a moment. It's important to point out also that AST/ALT elevation did not rise above 10%. GI events overall were limited and transient. Here we're seeing All diarrhea treatment emergent adverse events set against in the light gray, the time on treatment in both dose cohorts. The diarrhea AEs are superimposed on the time on treatment. There are no dose reductions or interruptions from treatment-related diarrhea. As you can see by the swimmer plot, almost all of these cases are transient, brief, self-contained episodes that resolved. Couple of these cases I want to go into a little more detail on. First, at 50 mg, the patient at the top with long-standing intermittent diarrhea. This is a patient who had over a 10-year history of diverticulosis and diarrhea prior to study entry, and also a 10-year history of intermittent use of IMODIUM. Another case I want to point out is at the 60 mg dose, the Grade two diarrhea. This was a diarrhea event considered unrelated to study drug and related to GLP-1 usage. Now turning to the efficacy data. 60 mg demonstrated strong clinical activity, and there was a clear dose response between 50 and 60 mg. The overall response rate at 60 mg was 79%, and the best overall CR rate was 64%. There was one patient who had a PR at the three-month assessment that converted to CR at the six-month assessment. At 50 mg, you can see once again a clear dose response with a CR rate of 33%. I want to point out as well that all patients who had three-month CRs maintained that CR at the six-month assessment time point. We're going to look into these data in a little more detail here with swimmer plots clearly showing evidence of response maintenance and maturation. Here we're seeing a swimmer plot in order of patient enrollment on the study and also looking at baseline pre-resection number of lesions and the number of marker lesions post-resection. Zeroing in on the 60 mg dose, you can see we had two patients with CRs at the three-month time point that were maintained at the six-month cystoscopy assessment. In addition, we had that one patient who had a PR at three months who converted to a CR at the six-month assessment. There was another patient who had a PR at three months. Unfortunately, this patient, who had a history of kidney stones prior to study entry, had multiple hospitalizations due to kidney stones and complicated UTIs. These were not related to study drug, and that patient had to be discontinued from the study due to lack of compliance with dabogratinib. I want to move on and discuss some initial data from our SURF303 study evaluating the use in upper tract low-grade urothelial cancer. This is a cancer, a cell type that is the same as that in low-grade intermediate-risk NMIBC, but due to its location in the ureters and kidney, presents particular problems with management and unfortunately sometimes results in kidney removal. This is our patient who was first, our first enrolled patient on the trial, was enrolled at the 60 mg dose. Patient has a substantial number of comorbidities, including type 2 diabetes, coronary artery disease, multiple ocular conditions, and the patient had multiple prior treatments, as well as gemcitabine, with a renal pelvis lesion of 5 mm at the first assessment. At three months, patient had a complete response and had no on-study AEs and no significant changes in lab values from baseline. This adds to our understanding, showing the tolerability and efficacy associated with the 60 mg dose. Thanks, Doug. I'd now like to talk about how we can use the data we're seeing today for our dose selection in a phase III adjuvant study. First off, we looked at a major driver of efficacy being AUC exposure. We had identified a target of an IC50 of 2,500 as being a key target we wanted to cover. When we look at the 26 patients across all the doses, 50 and 60 mg, and those that cover that IC50 and those that don't, we see a clear distinction in efficacy. 86% best overall response and a 71% CR rate for those that hit that AUC coverage of 2,500 versus a CR rate of 25% for those that don't. This allows us now to model, using the 172 patients who have had dabogratinib and had PK measured, an extensive population PK model highlighting that the doses we have chosen are in the steep part of the dose response curve. Once we get to the 60 mg, the vast majority of patients are hitting that AUC target and expected, as we are seeing, to potentially be in a response. There is a second driver that is also very important, and we touched on this in the beginning. Clinical activity clearly improves in patients with a single marker lesion. You can see here on the left, 50 and 60 mg dose pooled, but then broken down for those patients who had the THOR-2 like criteria of only a single marker lesion. We are seeing excellent activity. Best overall response of 94%, a CR rate of 56%. For those patients with multiple marker lesions, we see a degradation of that at only a 40% ORR. It is important to point out for those patients that are responding, those are the patients that have some of the highest AUC. They are all covering that 2,500 ng times hour per ml. It is also important to point out, of those patients that did not respond, six of the seven were these multiple marker lesion patients. We now, with this information, really have a clear answer, one that we did not know before, which was if we were to have run a study like THOR-2 with just a single marker lesion, might the data have looked differently? We can apply that lens here and see clearly that indeed, we see a better response at the 60 mg dose, 100% ORR. Our CR rate maturing to 75%, really hitting that benchmark we wanted to see and giving us a high degree of confidence that 60 mg should be the go forward dose in this adjuvant setting. Adding to that confidence is our modeling of the actual endpoint that is measured in an adjuvant phase III. This is, for us, a disease-free survival curve, and we are leveraging the data from Dr. Meeks and that 16 months median PFS to showcase that on placebo, the expectation is the population, 64% of patients would recur and 36% would remain tumor-free. We can now apply the activity we are seeing to that 64% of the population that is at risk and, taking certain assumptions of the CR rate and durability, start to project some scenarios. In the most conservative scenario, if we were to pool all doses, 26 patients, the CR rate we are seeing across 50 and 60 mg is 50%. If we were to take a very conservative duration applied to that 60%. Why is that conservative? Remember, three studies now, including ours, have demonstrated that as long as FGFR3 suppression is maintained after a CR, the durability is 100%. Now, we have not measured all patients out to 24 months, but it is a clear signal that durability should be good. Even in this very conservative scenario, we would land at a DFS of 55% with an implied hazard ratio of 0.6. That would be a successful phase III study. Additionally, we can look at the scenarios. The 60 mg dose, applying that CR rate of 64%, a durability of 80%, applying the PR rate of 14%, and a discounted durability, we would get to a 72% DFS. Now let's take the THOR-2-like design, which would be the single marker lesion patients at 60 mg, 81% projected DFS. Taken together, these data suggest across the board, we have a high probability of success and potential best-in-class efficacy that we could deliver in these patients with the data that we're seeing today at 60 mg. I'd like to now just spend a moment talking about what is the potential for these data to transform the standard of care. Recall, the market today is segmented in two important ways. For those patients who are seeking treatment with repeat catheterizations and installations, we have an opportunity to win on efficacy and convenience with oral dabogratinib. They've got instrumentation fatigue, and potentially replacing this intravascular approach with an oral could be a game changer. We see recent evidence of a case study that's highlighted just how this is happening today in the urologist office. Orgovyx is replacing a 35-year entrenched player of generic Lupron. That is occurring because, one, the mode of administration is excellent, but that Orgovyx and the commercial team have aligned the practice economics so that community urologists, through in-office dispense contracting and limited distribution, can participate in the economics with an oral just like they do with Part B. It's also streamlined the operations significantly for their offices as well. Orgovyx is doing over $1 billion and is projected to grow 80% next year. This is a great commercial success, and it highlights how we might think about the oral commercialization for dabogratinib in this setting. But it's not just this small population that's currently seeking treatment. There is this very large population, 70%, that's waiting to recur. For this population, we can offer an oral to reduce recurrence in surgery, potentially even reduce the three-month cystoscopy burden. Taken together, this is a really large opportunity, and it's highlighted by the patient surveys we've conducted, shown here. The number one appeal that patients highlight about the value of an oral drug is greater privacy. Patients are looking to take control of their disease. They're sick of having to drive to the office, have family members drive them to the office. They're sick of the discomfort associated with catheterization, the travel time, the time away from work. Oral dabogratinib has the potential to really resolve some of these key issues. When we've asked patients about the value proposition of an oral, even if they still need three-month checkups with cystoscopies, 77% agree the value proposition is still very strong and very large. Now, we've also surveyed urologists, and the overwhelming feedback has come back. Urologists would recommend patients try an oral before a Pretzel and other catheterization techniques. Why? Because they've actually highlighted that the biggest unmet need for their patients is the repeat catheterizations and the invasive experience. Even more so than the need for a durable response and reduced recurrence. It's seeking to reduce this over-instrumentation paradigm, and oral dabogratinib has that potential to do just that. Taken together, this is a very large opportunity. It's a $5+ billion market. We have, with the safety, potential chronic dosing, the efficacy, and the convenience of an oral, the opportunity to be a clear first-line choice for all of these patients. Now I'd like to hand it over to Dr. Mark Silva to share his perspective as an investigator and as a community urologist on the data that we've shared today. Dr. Silva? Thank you, Todd, and thank you for inviting me to join you today. I am a practicing urologist. I am a community-based urologist and investigator in both the SURF 302 intermediate-risk NMIBC study, as well as the SURF 303 low-grade UTUC study. Intermediate-risk NMIBC is one of the most common diseases we treat, but it's also one of the most frustrating. It's a recurrent disease, but it's not a progressive disease. Patients often live with a recurrent disease for years. They undergo repeat cystoscopies, surgeries under anesthesia, intravesical treatments, repeated catheterizations, and bladder instillations. They come to the office once a week for six weeks. Their urologist is one of their best friends, and they know all the staff here for those reasons. In my experience, the biggest barrier isn't the patients don't want to reduce their risk of recurrence, they just don't want to go through the treatment process. They don't want to go through the journey that's currently available. That's why I find both these studies, as well as the data, very encouraging when it comes to Tyra and the dabogratinib. Oral dabo, it demonstrated meaningful clinical activity, together with favorable safety profile and just a very easy mode of administration. Every week, every day, I have conversations with patients who are hesitant to undergo repeated intravesical therapy. It's a hard sell for patients to come in for similar treatments that they get for high-risk disease. They end up choosing surveillance instead of treatment because the options are invasive and difficult to live with. They have to leave work. They have to miss school. They have to miss their life. They decide to live life, but essentially waiting to recur instead of going for treatments. When it comes to oral dabo, if we had this effective oral, well-tolerated treatment, it would be changing the conversation that we have with patients pretty significantly. When it comes to an effective oral option, this could empower patients, giving them more control over their disease and treatment. As you discussed beforehand, it's the privacy. You could take a medication at home with your regular statin and your aspirin, instead of coming in to get a catheter placed and exposing yourself in the office. It's just a difficult life to go through. I think all of this, the data, the ease of administration, this is all a meaningful win for patients, providers, and our healthcare system. From a clinical trial perspective, I also find the planned phase III strategy very compelling. It's going to be very exciting, and we've already gotten approved to be a site, so we're very excited for that. An adjuvant study evaluating a well-tolerated oral therapy in this patient population addresses a very real unmet need, as we've discussed, and I believe it will resonate with both physicians and patients. It's exactly the kind of study I'd be excited to offer in my practice, and it's going to become part of our practice, not just from my solitary practice, but as a 18-urology practice across the board. When it comes to FGFR inhibition, it's going to be very exciting to see it both as bladder as well as upper tract. Although a more rare disease, it is something that it's going to be very exciting to not have to say, You're going to go for a large robotic surgery to take your kidney out, versus taking, again, an oral medication in the privacy of your own home. So obviously, additional follow-up with larger data sets is going to be on the horizon. But as someone who treats these patients every day, I think that oral dabogratinib is going to be very revolutionary in the low-grade, intermediate-risk NMIBC, and it's going to become a very big part of our practice going forward. So I'm going to turn it back over to Todd at this point. Thank you, Dr. Silva. Appreciate those very helpful perspectives. Just to close up here, want to talk about next steps. The clinical momentum continues, as you've seen today, on our dabogratinib 3x3 strategy. We now have our first clinical proof of concept, a selected dose of 60 mg that we're going to be potentially moving forward in an adjuvant phase III. We're going to engage FDA on these results and that phase III design as a next step and prepare to initiate a study next year. Additionally, we now are really excited to see this first patient respond in UTUC at a 60 mg dose, achieving a CR. It's great demonstration of initial activity. There's more patients and multiple doses. Here are 60 and 80 mg doses to evaluate in a supelative setting. So you can expect that we'll have initial results across these doses next year in 2027. Finally, I'm excited to announce as well that we've now cleared our dose level five with no safety signals. That allows us or sets us up that in Q1 of 2027, we'll have the first 25 patients across five different dose levels in sentinel participants with six months AHV to report out. So with that, I'd like to hand it back to the Operator, and we'll take questions. Thank you. If you would like to ask a question, please press star one one. If your question has been answered and you would like to remove yourself from the queue, press star one one again. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open. Hey, guys. Good morning. Thank you very much for the presentations and the thoughtful discussion. Maybe one for Todd and one for Dr. Silva. Todd, it is clear that single marker lesion patients are closer to the adjuvant patients with zero lesions that will be treated in the phase III. Can you discuss the rationale as to why a marker lesion study of this design was employed in phase II, and also what the THOR-2 experience tells us about how the CR rate should trend over time? Dr. Silva, I know you touched on some of this already. Can you elaborate on what enrollment was like in the SURF302 study based on your experience and what you anticipate phase III enrollment will look like so we can get a better sense of patient demand versus alternative therapies? Thanks, Tyler. Let me tackle the first question. A marker lesion study is a very unique study. It gives you the opportunity in a very short amount of time to understand whether you have enough drug on board for an adjuvant setting, rather than waiting 24 months for patients to recur. By leaving a small marked lesion and seeing it disappear and shrink, you have an opportunity to know that your dose will essentially be effective for the adjuvant setting. Now, there are five programs that are moving into late-stage development. Three of them moved forward without even running a phase II. It is really only us and J&J that have employed these marker lesion type studies to move forward. THOR-2 was designed with a single marker lesion, and you see the efficacy, really benchmark that we have talked about. We designed a study that has both single marker lesion and multiple marker lesion and allows us to get a broader understanding of the drug at the dose that we are testing. For that single marker lesion comparison, we are seeing the THOR-2-like efficacy that we wanted to see. Investors will recall, we have said for months now that if we could hit THOR-2-like efficacy with a superior safety profile that we are sharing today, that would be lights out data. It would be lights out data because we would have a dose to move forward with an oral, and it is something that no one has been able to do before. THOR-2 was shut down as a study because of the tolerability, and it moved to the Pretzel, the TAR-210. Really, that is the only other study now that has run a phase II and is now moving into phase III. All of this combines to allow us to now project a high likelihood of success when we model the actual endpoint in phase III, which is a disease-free survival. When we look at our 60 mg dose, really in all of these scenarios, we can now move forward into a phase III with a very high degree of confidence given the data set we have. Now, of course, we need to talk to FDA about that, which is the immediate next step. But this really puts us in the best position with the breadth of data that we now have pointing to both the dose, the placebo effect, and the likelihood of success in phase III. With that, let me hand it over to Mark to answer the second part of the question. Maybe just one more thing before I do that, though. One question we get a lot, and it is really important. When you think about the THOR-2 efficacy, a lot of investors sort of expected an 89% CR rate out the gate. And we spent a lot of time over the last few months educating folks that the actual three-month CR in THOR-2 was 72%, but then it matured over time to 89%. That is exactly what we are now seeing in our data as well. CRs persist, and PRs convert to CRs. That is really important because the best overall response today we are seeing today is not the best overall response that we will see tomorrow as we watch PRs. And if they mature, convert to CRs, the data actually mature towards the ORR. So that is a really important distinction. We can, in this initial time point, see that we have got a dose. But of course, over time, we will see the durability and the maturation. But we can make a go-forward decision, which is what this study was designed for. So yeah. Let me hand it over to Dr. Silva now on the questions you had about running the study. Hey, this is Mark Silva here. So for regarding the enrollment in the study, always enrollment in clinical trials is usually kind of a discussion and in-depth with the patient, learning about the protocol and learning about how to enroll and what enrollment and being on study means, the idea of taking an experimental drug, and then all the visits that kind of come on with that, because there are a lot of visits. I have had almost the exact opposite situation with enrollment in the studies. These patients, again, this is the experience. I am trying to push the experience of these patients. They go for surgery. They come in for treatments. They are getting a catheter in the bladder. They are getting medication put in the bladder. They are holding it for an hour. They are going home. They are missing work. They are coming in for invasive procedures. These patients have had resections, have had biopsies, had fulgurations. They've had their urethra violated. They can have strictures. They can have contractures. They can have lower urinary tract symptoms. All of these symptoms and all of this discomfort leads patients to say, Yes. When I say there's an oral medication that we can use, I barely get that sentence out and they're like, Sure, I'm in. Because, again, it is the patient experience. I haven't discussed with them the oncologic data or the reason or the reason for the study, the FGFR mutation. The patient is in. When they hear that they are either an FGFR mutation positive or negative, they're excited to go on study. The ones that, and they're rare, again about 5% of patients, 5%-10% of patients are FGFR negative they come back and they're sad. Why? Because they have to go for a procedure. They have to go for a procedure to resect out their the tumor. So enrollment in this study has been exceedingly easy because the other options are just so uncomfortable. They're just such a tedious task. So it's really been an ease of enrollment onto the study, and that discussion with the patient and their experience is really kind of driving that ease of enrollment. Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is open. Hi, good morning. Congrats on the update, and thanks for taking my questions. Wondering, just as the data mature, when should we expect to see longer follow-up data from this cohort of patients? What could the cadence of updates look like going forward? How do you expect the durability to shape up compared to intravesical treatments? Yeah, thanks, Maury. The most important next step for us is to take this data set to FDA and align on our phase III protocol design. That is really the next year opportunity when we are moving into phase III to highlight that alignment and that ultimate design. As we go, though, this study is designed to have patients on treatment out to 24 months. We are going to be enrolling 30 patients at the 60 mg dose. You can see that we already have, for safety, 22 enrolled, so we are nearly there. We will be able to follow those patients out for that entire 24 months. As we move forward with alignment with FDA on the phase III protocol, there will be an opportunity at that point in time, prior to launching the phase III, to talk about maturation of data, and as we go even further, following these patients out to 24 months. Got it. That is helpful. Maybe a question for Dr. Silva. From the safety signals observed in this population, which one do you think needs to be most closely monitored in practice? Maybe for the company, for the 36% fatigue you are reporting in the 60 mg cohort, can you elaborate on whether that is chronic or transient? So far, the patients who have been on study with me, I have not had many adverse events or any issues. I think, when you had asked about the fatigue, it is a minimal amount and it is transient. It is usually the first couple of days that they start the medication, and then I have people who have been on it for a couple of months, and they are saying, It might have been that I had a lot of stuff going on. I was traveling to and from. So it is not any sort of fatigue that is disease or medication changing. Got it. Okay. Thanks. Thanks for taking my questions. Yeah, in terms of the fatigue we're seeing on study in terms of the data, it's a mixed picture versus transient versus chronic. But once again, it's an open-label study. In placebo studies in these type of populations, you're seeing these rates of fatigue. In open label study, this kind of data is difficult to interpret. We haven't seen this signal with the programs to date. Got it. Thank you very much. Thank you. Our next question comes from Chris Raymond with Raymond James. Your line is open. Hey, thanks. Maybe a question for management and also one for Dr. Silva. So maybe first, Todd, before the study was published at AUA this year, I think the thinking was that a placebo disease recurrence rate at 24 months would be about 60%. This new data obviously refines this to just FGFR3-positive patients. Just reading the study, it looks like they measure low-grade and intermediate-risk patients. Maybe just walk us through the math from the study that gets us to that 36% at 24 months. Any sort of commentary as to how you feel this will hold up with subsequent studies when those are done looking at just TURBT alone. Then a follow-up for Dr. Silva. Yeah. Thanks, Chris. It's a great question. I think there were a few brand-new pieces of information that we shared today in addition to our data, and this was one of them that we're now talking more about. This was a relatively large study. It's actually the largest, most controlled prospective data set that we have now around the precise population we plan to treat in phase III. Low-grade, FGFR3-positive, intermediate risk, NMIBC. Even when we look at maybe some of the other phase III data sets that we've read out, for example, CG Oncology's observation arm, it's not going to be as pure of a signal as this is for us in anticipating what we might see in a placebo. Now, some of these patients could have gone on intravesical maintenance chemo, but as you know, that would've been a relatively small proportion. That would only degrade the data further if intravesical chemo and maintenance had an effect. You translate this median 16-month recurrence-free survival in a simple logarithmic exponential algorithm, and we have that highlighted on our slide 20. That's what essentially gets you to the 36% at 24 months. It's the typical model, the exponential model you would apply in these Kaplan-Meier curves with that 16-month RFS is how we get there. Thanks. Then a follow-up for Dr. Silva. I guess back also to that AUA study from May. It is pretty striking how poorly FGFR3-positive patients do from this data. Did you have an inkling in your practice of this difference before that data? So across the board, this study that you are mentioning specifically was testing FGFR-positive people. FGFR positivity is not actually routinely checked across our practice. I do not actually know too many specific vendors that do FGFR testing specifically. That is becoming more popular. FoundationOne has now an FGFR mutation test, and we are actually working to bring it in-house into our practice, across not just our practice, but our larger consortium. Because this is data that we do want to know. The data shows FGFR-positive people have worse recurrences or higher risk of recurrence. So we want to know about these people earlier, and I think that is good data for the Tyra medications out there, because we do want to escalate care when it is needed. So, if we test more for FGFR mutations, then we would be able to potentially get more patients on the medication. Thank you. Thank you. Our next question comes from Brad Canino with Guggenheim Securities. Your line is open. Morning. I am really trying to understand this interplay between the three-month CR and a two-year adjuvant study. I am wondering how much of the phase III DFS effect size is expected to be captured in year two of the therapy, where presumably only a safe oral drug can be given for those extra months of 13 to 24. Depending on your answer, it gets me very curious about how much follow-up from the full 30 patient, 60-mid cohort you can show next year to demonstrate that the CRs and the tolerability are maintained beyond year one. Thank you. Yeah, thanks, and great questions. We heard repeatedly from physicians, this is all about tolerability and durability if you are going to think about the maintenance of a chronic dosing regimen with an oral. You have highlighted something really important, which is our plan is to treat all the way through 24 months to have a sufficiently tolerable, chronically dosed oral. The direct competitor or comparison in the FGFR3-positive space is erdafitinib and TAR-210. Their phase II and now their phase III had treatment for one year, and then the patients come off treatment. We are already seeing, as they highlighted in their initial phase II data and in THOR-2, that if you take patients off of FGFR3 suppression, the recurrence rate appears to come right back online quite quickly. So if you combine Meeks data now, and you look at that high rate of recurrence kicking off in call it months 13 to 24 if you are not maintaining the suppression, you can imagine how an intervention that was only designed because of the burden of installation to work for 12 months could derate very quickly in the pursuing 12 months. An oral has this opportunity to treat across chronically for that 24 months and then ultimately win on efficacy when you start to look at the long-term outcomes, which is what patients care about most. On the data update potential in terms of follow-up for the next few disclosure? Yeah. So of course, as I mentioned, this is a study that will follow these patients out to 24 months. There will be plenty of opportunities to provide data updates, maturity, again, additional N on the efficacy evaluable, because we'll go up to 30, and then timelines all the way out to 24 months. So expect from us, of course, next year, certainly around a phase III start after alignment with FDA, an opportunity there. But you could imagine every year this goes on, we'll have an ability to really speak to the metrics around durability that we're seeing, conversions of PR to CRs maintaining. All of that can then feed back into our model to predict phase III success. And we'll be able to do that in real time while we're kicking off the study and enrolling patients. Yeah. And then beyond bladder, I mean, so you have a very safe dose that covers IC50. What do you think that means for development of achondroplasia? That's it for me. Thanks. Yeah, great question. And obviously, we're really pleased that we've now cleared dose level five, and I'd say us coming right in line with the target engagement we hoped for at these doses just gives us confidence that our translational models are working, that we can predict the right types of doses to be testing, and we feel confident that the five doses we have, where the safety's been excellent so far in the kids, has the potential to really hit that endpoint we're looking for, which is improved initial annualized height velocity, which could ultimately translate to meaningful clinical outcomes for these kids. Thank you. Our next question comes from Sami Corwin with William Blair. Your line is open. Hi. Thanks for the data update this morning and for taking my questions. I have one for Dr. Silva and one for Todd. Dr. Silva, I guess, do you agree with the interpretation of the marker lesion data, and would you have expected patients with a higher number of marker lesions to not respond as well? Continuing off that last question, Todd, how are you thinking about the way through to achondroplasia here, and, keeping in mind that achondroplasia patients don't have marker lesions, would you expect the exposure of dabo to translate in the same way to achondroplasia, or would you think about exploring additional dose levels given you are seeing a tolerable safety so far at dose level five in achondroplasia? Thank you. So for the multifocal- Mark, maybe you could start? Yeah. Oh, yeah. Go ahead. Regarding multifocal disease, I mean, when it comes to bladder cancer, multifocality definitely always increases the amount of complexity when it comes to the patient. You have low-grade disease. If it is a small and solitary lesion, you are a low-risk patient. But if you have two lesions, then you are automatically an intermediate-risk patient. Of course, multifocality is going to add to the disease complexity and will make it more difficult for a certain amount of medication to manage that bladder. When it comes to the length of disease and the dosage needed, I think it is appropriate. I think that the data is similar to what data from other disease states and what TAR-210 shows for non-muscle invasive bladder cancer in a similar state. I think it is just that the multifocality adds to the difficulty of the disease management. Yeah. Thanks, Mark. Getting into achondroplasia, the key dose levels one through five that we have are really, again, hitting target exposures that translationally we think will potentially improve outcomes and efficacy beyond what the other treatments have been able to show in achondroplasia. The key thing that we are looking to avoid, now that we see such excellent safety across so many studies, we do not have a significant concern around safety from pan-FGFR activity with this agent. We have a very strong therapeutic index. Now what we are indexing towards is making sure that we are safe with our FGFR3 suppression. We do not want to get into a situation of suppressing FGFR3 so much that you can move to bone overgrowth. This is a toxicity that is seen in our animal models. We want to make sure that the exposure is not pushing beyond an IC50. It is certainly not pushing to the sort of IC90 suppression. We remain confident with all of the data that we are seeing that within the five dose levels, we should still be safe as it relates to growth. If we were to see anything, obviously we would manage that. But we are not really concerned with safety signals from what we have seen outside of overgrowth, and we think that the dose levels we have chosen should track us towards where we want to be on improving efficacy without pushing too far. Thank you. Our next question comes from Mazahir Alim ohammed with OpCo. Your line is open. Thank you for taking our questions and for the presentation this morning. I think just one for you, Todd, and then one for the physician as well. First, as we think about the PFS or the PRs turning into complete responses, I guess with the patients that haven't reached the three-month assessment, when those read out, are they weighted toward either dose or towards single versus multiple lesions? Of the three-month PRs at 60 mg, how many have reached six-month assessment? Then, as you think about clinically, how are these patients, and this is kind of something I'm just trying to wrap my head around. Assuming they get on the oral pill, how will routine cystoscopy still remain for these patients? Would this allow these patients to completely, basically get off cystoscopy completely, or will they still require a yearly surveillance cystoscopy in the background? Yeah. Thanks for the question. I think that we have that detailed swimmers plot in the presentation that we shared today. That shows you exactly where we're at today with the patients that have at least been on drug for three months. As you'll see from our safety data set, there are additional patients evaluable for safety that haven't quite yet got to three months. That total number was 22 at the 60 mg dose, for example. We're only reporting out 14 patients of efficacy because only 14 of the 22 had gotten to the three months. So that should give you a little bit of a picture of where the total patient population is within this study. Then, the second question you asked, I'm not sure I captured that. I was just thinking with patients and cystoscopies, after getting on treatment with these patients, once on therapy, if approved, would they continue to require any more manipulation or procedures? It's a great question. Recall that we did test whether the value proposition holds if you still need to do three months cystoscopy, and patients very much agreed that it did. But you could imagine a future where if we're bending the disease-free survival curve meaningfully, that the need for three-month evaluations could be reduced to six months, 12 months even. That's already happening in practice today. After a series of three-month evaluations, if you're not seeing recurrence, you start to look six months and then 12 months. In a future where patients are well managed with an oral, you could imagine that guidelines might adjust, physicians might adjust their practice to say, Hey, you have a really low likelihood of recurrence based off of the data, and therefore, let's look at you every 12 months, potentially going forward. That would be a huge additional advantage of an oral that really can't be achieved with any of the other intravesical approaches. Noted. Thank you so much. Thank you. Our next question comes from Robert Driscoll with Wedbush. Your line is open. Great. Thank you. Morning, guys, and congrats on all the data here. I wanted to ask about the ablative setting cohort that's going to be evaluated here at 70 mg. I guess, the expected number, size of patient lesions and really what you're going to be looking there for read-throughs to the phase III adjuvant study and maybe even the UTUC study as well. Thanks. Yeah. Thanks, Robert. As a reminder, we're just looking at the 70 mg for the ablative, not adjuvant. 60 mg would be our go-forward dose for adjuvant. Within this study, we have the option of opening an additional dose cohort up to 30 patients. That's exactly what we'll do with the 70 mg. We're going to be completing the enrollment in 60 mg quite shortly. While this study is open, this is an opportunity to then evaluate 70 mg, potentially for ablative. Now, we've talked about this before in the UTUC setting, where we said maybe a higher dose is needed to debulk tumors. This has always been a hypothesis. When we think about higher NMIBC, if you wanted to use a drug to debulk tumors, getting this data around 70 mg could be helpful. Now we think it's a much smaller part of the market. The broader market is going to be the adjuvant post-TURBT, post-evaluation of the lesions that have been removed to confirm that they're low grade and intermediate risk. You would go forward with an adjuvant treatment. In the ablative setting, there may be some patients that want to forego surgery and would be willing to take a treatment that does. A higher dose could be appropriate to debulk the tumors and, given that they're not having to go under surgery, there could be a benefit. But we expect this to be a relatively small part of the market and the opportunity. Just to be clear, we all heard in the UroGen ODAC, FDA had some concerns around the ablative approach and single-arm approach, and most people have moved to adjuvant because that registrational path is more clear. We would also want to get clarity on the registrational path before moving forward with an expansion in ablation after we get this data with the 70-milligram dose. Great. Thanks a lot, guys. Thank you. We have time for one more question, and that question comes from Allison Bratzel with Piper Sandler. Your line is open. Hey, good morning, and thanks for fitting me in. First, just a follow-up to Dr. Silva's comments about multifocality adding to complexity of disease management. For the company, could you talk to any considerations on whether this data on single versus multiple baseline lesions has any effect on how you define the adjuvant phase III population, just given the drug's activity was different between those populations? Then separately, mechanistically, what do we know about why PRs convert to CR at six months instead of three? Is there any relationship, or do you think there's any relationship between exposure level, time to conversion? Any clarity or thoughts there would be helpful. Thank you. Yeah. Thanks, Allison. On the first question, for your benefit, we actually highlight in the swimmer plot baseline lesions and marker lesions. When you evaluate that, one of the things you'll see is there are patients with multifocal disease, eight lesions that are cut out, brought down to one, that have a CR on our drug. So it's not so much what you started with, it's how many lesions you left behind that is a key driver of what we're seeing in the signal between single marker lesions and multiple marker lesions. This would've been the same for THOR-2. A single marker lesion doesn't mean that you only had one marker lesion at the start. Many of these patients did have multiple lesions at the start. It's just the debulking and then the remaining single marker lesion, which gives you the signal that you've got enough drug on board to be adjuvant. So for an adjuvant setting, the single marker lesion is the closest approximate, because in an adjuvant setting, you have zero marker lesions. You've removed all of the tumor. So the single marker lesion we anticipate being very predictive in the adjuvant setting, just like was sort of the hypothesis in THOR-2 and why we make that direct comparison. Now, why do PRs convert to CRs over time? An oral drug with systemic exposure is fundamentally different. We're getting at the tumor systemically, and the amount of drug on board that's sufficient to keep tumors from growing could take a little bit longer to shrink those tumors. We saw that in the THOR-2 data. 72% of patients had the CR at three months, and it took till month 12 to get to an overall CR rate of 89%. But the beauty of that data shows that a PR, that means your lesions shrunk more than 50% with no new lesions arising, is clear indication that the drug is working. Even if it takes longer in this ablative setting, in the adjuvant setting, you already have the signal at three months with your ORR that you have enough drug on board to be effective. So if we just look at our ORR across single lesions and multiple marker lesions, 79% ORR is highly predictive of success in the adjuvant setting. If we look at the single marker lesion, we're able to say, of course, we're hitting the benchmark of THOR-2-like efficacy because that's the lens through which THOR-2 was designed. Both of those data points are adding to a very high confidence moving into the adjuvant setting here. Thank you. We do have time for another question, and that question comes from Ellie Merle with Barclays. Your line is open. Hey, guys. Thanks so much for taking my question. Just from a safety perspective, can you elaborate on the transaminase elevations and what was seen in the study overall versus what was deemed treatment-related? I guess your confidence in the safety profile, particularly as it relates to both NMIBC, but also achondroplasia. Thanks. Yeah. Thanks, Ellie. Let me have Doug answer this question. Sure. We're extremely encouraged with the overall safety profile. The toxicities related to transaminase elevation, as you can see by the table, there's a cutoff of 10%. We're dealing with low frequencies of transaminase elevations overall. It was a very good sign at this point that we haven't seen this being a major safety issue so far for patients on treatment. Yeah, Ellie, ultimately, we think that translates very well. As we talked about, no safety signals through that dose level five. We remain very confident on the therapeutic index for the doses we're testing in achon. Great. Thanks. Thank you. This concludes the question- and- answer session. I'd like to turn the call back over to Todd Harris for closing remarks. Thank you, thank you everyone for participating today. We are absolutely thrilled with what we are seeing. For the first time, we have this really deep data set across multiple efficacy evaluable and safety evaluable patients with dabogratinib in this population, predicting a really high likelihood of success of moving our 60 mg dose forward in the outpatient setting. This, we believe, will be a paradigm shift and a game changer for patients, 70% of which are voting with their feet today to not undergo intravesical urethral violation for effective treatments. Offering an effective treatment that is in oral, we believe will absolutely change the game. We are thrilled about our path forward to move this into a phase III next year and to continue to obviously monitor this data, and for our broader dabogratinib 3x3 strategy with the important data points that are going to be coming up in achondroplasia as well as additional patients in UTUC. This is really the first evidence across the dabogratinib 3x3 strategy. We have got our proof of concept, we have got our dose, and we are excited to move forward. Thanks, everyone, for joining. Look forward to following up with many of you one-on-one after this. Thank you for your participation. You may now disconnect. Good day.