Good day, ladies and gentlemen, and thank you for standing by. Welcome to the TYRA Biosciences Conference Call to discuss the first patient dosed with TYRA-300 in the SURF-301 study. As a reminder, this conference is being recorded. Now I'd like to turn the conference call over to Amy Conrad from Investor Relations. Please proceed. Thank you, Jamie. Good morning, everyone, and thank you for joining us. With me today from TYRA are Todd Harris, Chief Executive Officer, and Hiroomi Tada, our Chief Medical Officer. Also on today's call is Dr. Jonathan Rosenberg, Chief of the Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, and the Enno W. Ercklentz Chair at Memorial Sloan Kettering Cancer Center. For those of you participating via conference call, the slides are made available via webcast and can also be accessed by going to the investor relations page of our website following conclusion of today's call. Todd will provide introductory remarks and will review the outside market opportunity for TYRA-300 in bladder cancer. Hiroomi will discuss our clinical plans for TYRA-300 with SURF301, and Dr. Rosenberg will provide context on the patient journey and unmet needs in bladder cancer. We will open up the call for your questions. Before we begin, I would like to remind you that this call will contain forward-looking statements concerning TYRA's future expectations, plans, prospects, corporate strategy, and performance, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our filings with the SEC. Any forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements. I'll turn the call over to Todd. Todd? Thank you, Amy. Welcome, everyone, and thank you for joining us. Right now is a really exciting time at TYRA. We initiated our first clinical study, SURF-301, and have dosed our first patient with TYRA-300, our FGFR3 selective inhibitor designed to be agnostic to the gatekeeper mutation. This is a significant milestone for TYRA, which marks our official transition to a clinical stage company. As you can imagine, with the achievement of this milestone, our conviction in TYRA-300 continues to grow. It's the first program stemming from our in-house SNAP chemistry platform, which is purpose-built and designed to overcome tumor resistance in oncology. Our platform is rich in opportunity, and each one of our assets was designed to be best in class within their respective indications. TYRA-300 represents our largest opportunity with blockbuster potential in bladder cancer. To help frame out this opportunity, we're excited to have Dr. Jonathan Rosenberg joining us on the call today. Jonathan is a world-renowned GU medical oncologist and key opinion leader who has run some of the most important clinical trials in bladder cancer, including for emerging targeted therapies. He will touch on the broad opportunity of FGFR3 agents in bladder cancer, the overall patient journey, and the current approaches to address the unmet medical needs. With that, I'll turn the call over to Jonathan. Jonathan? Thank you so much for the introduction, and it's a pleasure to be here to talk about FGFR3 and bladder cancer. The FGFR3 protein is mutated across the spectrum of disease states in urothelial cancer, both in upper tract and in bladder tumors. It is quite common in up to 70% of non-muscle invasive bladder cancers, particularly non-invasive tumors. These tumors frequently recur but rarely progress, and actually represent the most common form of the disease, for which there is no targeted therapy that is approved. In part, because the toxicities of existing treatments prevent them to be used regularly in patients with non-muscle invasive disease. For muscle-invasive and metastatic bladder cancer, mutations and fusions of FGFR3 occur anywhere from 12%-20% of patients, depending on the trial, depending on the dataset you look at. This has been validated as a clinical target in an urothelial cancer based on data from erdafitinib, which I'll talk about in a few minutes. Also, a significant unmet need is upper tract urothelial cancer, which have very high rates of FGFR3 mutations, about 92% of low-grade tumors and 60% of high-grade tumors. The standard of care for many of these patients is nephroureterectomy. While people can live with one kidney, it's better to have two. An agent that would be able to target this alteration might lead to clinical benefit, and reduction in need for invasive surgeries in patients with advanced with locally advanced upper tract disease. Next slide. FGFR inhibition has been shown in several trials to be active. We see here data from infigratinib, or formerly known BGJ398. This is a study in advanced urothelial cancer status post patient status post platinum chemotherapy. We see that, with this agent, the response rate was 25%. Many of these responses were durable up to a year, and that there was activity regardless of the type of mutation or alteration that was observed. This drug has not been approved in urothelial cancer but is now approved in other indications, but represented the first completed trial that showed data that the target was relevant. Next slide shows the erdafitinib data from the pivotal trial that led to the accelerated approval. This is from BLC2001, showing that 40% of patients responded to erdafitinib with confirmed response, with a progression-free survival and overall survival of 5.5 and 13.8 months, and that many patients were on treatment well past one year. We have not seen the data updated again in manuscript form, and we await the randomized phase III trial data from this agent to see whether or not this will receive full approval. These data supported the first FDA approval of a targeted therapy in advanced urothelial cancer. Next slide. Unfortunately, pan FGFR inhibition, which is what an erdafitinib is and what infigratinib is, lead to many more side effects than one might expect with a selective FGFR3 inhibitor. In particular, these are toxicities associated with erdafitinib, central serous retinopathy and retinal pigment epithelial detachments, which are generally reversible, do occur in about a quarter of patients. Diarrhea is common. Fingernail changes, while not serious or life-threatening, certainly are uncomfortable, and having patients lose their fingernails is a quality-of-life impediment. Stomatitis with FGFR3 inhibitors has been very difficult to manage, and while again, not necessarily life-threatening, remains a substantial detriment to quality of life. In addition, the electrolyte abnormalities that result from pan FGFR inhibition, including hyperphosphatemia and hyponatremia, can limit treatment for patients who receive these agents. While these may be manageable, certainly require more attention from the physician and the patient, and significant dietary changes to be able to stay on medication. Next slide. There was a pilot study that we conducted at Memorial Sloan Kettering with infigratinib as a infigratinib, sorry, as a treatment for non-muscle invasive bladder cancer. It was a marker lesion pilot study that ultimately only was able to recruit four patients. I think the study was before its time. Interestingly enough, we saw ablation of tumors in three out of four patients who received FGFR3 inhibitor for a period of about 9 weeks prior to their first assessment. I think this establishes at least proof of concept that in a non-muscle invasive bladder cancer setting, that an oral agent that's an FGFR inhibitor would have activity in non-muscle invasive bladder cancer, and I think leads us to potential future opportunities. What we also saw in those patients was that toxicity was difficult, and that all the patients essentially came off for toxicity rather than treatment failure. The longest treatment was about four months or so. I think with that kind of sets the stage for where we are with FGFR3 inhibition in urothelial cancer. I'll turn it back over to Todd and Hiroomi. All right. Thank you, Jonathan. We founded TYRA with a simple mission to discover and develop next-generation drugs in targeted oncology to deliver benefit of patients and to patients. On slide 12, we're showing an example of one of these patients that developed resistance to currently available therapies. This patient had an FGFR2-positive intrahepatic cholangiocarcinoma. They were given infigratinib. They saw a nice initial response, but ultimately that patient recurred, and with the recurrence coincided a single amino acid shift. As you can see on slide 13, this single amino acid shift occurred in the active site of the FGFR2 protein, which you see here is where infigratinib binds in the back pocket. The gray space filling model represents the large steric side chain of the phenylalanine cutting through the dimethoxyphenyl moiety of infigratinib, and this is the gatekeeper mutation, and it significantly reduces infigratinib's potency. This issue is not isolated to infigratinib. All of the approved pan-FGFR inhibitors have used the same dimethoxyphenyl moiety to access the back pocket. As a result, all of these agents have a liability for gatekeeper mutations, which has now been seen clinically in many patients. As we move to slide 14, we'd like to highlight this isn't a new story. We saw the resistance story emerge with EGFR therapies, where the first-generation drugs achieved progression-free survival of about 10 months, but then patients recurred with the T790M gatekeeper mutation in the back pocket. osimertinib was designed to overcome this and was able to rescue patients who recurred after treatment with first-generation inhibitors. In the head-to-head studies, it nearly doubled progression-free survival to 19 months, which was encouraging to see. On slide 15, we really highlight in the last five years, we've seen that extended progression-free survival repeat across multiple targets, most recently with repotrectinib. ROS1 is a target by addressing the resistance of the first-generation drugs by improving tolerability. The FGFR agents in development are showing limited durability improvements over the prior generation. We know there is a huge opportunity to do so by addressing acquired resistance. TYRA-300 was designed to overcome both the major limitations of first-generation inhibitors, with selectivity for the gatekeeper mutation and with selectivity for FGFR3 over other isoforms. As we move to slide 16, we want to highlight that we believe an FGFR3 selective inhibitor, like TYRA-300, has the potential to address an outsized market opportunity with accounting for key factors that drive precision oncology revenues. Returning to the osimertinib example, in non-small cell lung cancer, as you can see on the top row here, there are nearly 200,000 incident patients in the United States. Around 15% of those patients have the EGFR mutation, most of whom are eligible for treatment with osimertinib now that it is an approved agent in the adjuvant setting. With its efficacious and well-tolerated profile, adjuvant patients stay on therapy for close to two years on average, and these factors have combined with leading market share resulting in $5 billion in 2021 sales for osimertinib. Alectinib is approved for front line metastatic non-small cell lung cancer. With only around 2% of cases driven by ALK alterations, this therapy still generated around $1.5 billion in 2021 sales. Now as we go to FGFR3 and urothelial cancer, there are approximately 80,000 incident patients in the United States with urothelial carcinoma, and it's estimated about 50% of these patients have an FGFR3 activating mutation. Based on annual incidence and percent alteration alone, it is clear that the opportunity for an FGFR3 selective agent like TYRA-300 is outsized relative to other oncology targets. As we move to slide 17, though we are initiating TYRA-300 clinical development in late stage patients, we believe there is significant opportunity to serve unmet needs in earlier stages of the disease using an FGFR3 selective agent. In the intermediate and high risk non-muscle invasive bladder cancer setting, 25%-30% of patients treated with adequate intravesical chemotherapy and BCG have been shown to relapse within a year from treatment. Outcomes for many patients treated with less than adequate therapy are worse. BCG resistant patients can be treated with the immunotherapy, though many are ultimately referred to an oncologist for cystectomy or bladder removal. Patients with muscle-invasive bladder cancer can be treated with neoadjuvant or adjuvant chemotherapy, ultimately 30%-50% of radical cystectomy patients will relapse with metastatic disease. Toxicities remain a challenge across the metastatic setting, including chemotherapy, ADCs, erdafitinib, and emerging PD-1 ADC combinations. Patients who relapse from erdafitinib have no targeted option to address the commonly arising gatekeeper mutation. We believe an efficacious, well-tolerated small molecule FGFR3 inhibitor has the potential to meaningfully address unmet needs across the stages of the disease treated by both urologists and oncologists, either as monotherapy or as part of a combination regimen. We have alignment with the FDA that after establishing initial proof of concept of safety and efficacy in late-stage patients, we can open up earlier-stage NMIBC cohorts. With that, I'll turn the call over to Hiroomi to discuss TYRA-300 and SURF-301 in more detail. Hiroomi? Great. Thanks, Todd, and good morning, everyone. I'm really excited to discuss our lead candidate, TYRA-300, which is the first oral FGFR3 selective inhibitor in development today for urothelial cancer. As Todd mentioned, TYRA-300 was de-designed using our SNAP chemistry platform to be selective for FGFR3. This is actually a challenging engineering problem that we set out to solve because the amino acid sequences from the active sites were actually nearly identical. We started by overlaying the molecular models for FGFR1 and FGFR3 and identified subtle areas within the active site where we felt that we could drive higher FGFR3 selectivity over FGFR1. This was followed by dozens of candidates that were co-crystallized in high-resolution structures of the various FGFR family members. What you can see on the right is a cross-section of one such area where we were able to push deeper into the pocket of FGFR3, where FGFR 1 was more constrained. We did this in multiple areas of the active site, that led to greater selectivity for FGFR3 over FGFR 1. On the next slide, what you can see is the result of all of this work, in the profile for TYRA-300. We do a lot of competitive profiling, and it's critical to our next generation candidate design process. This slide shows that using a collection of Ba/F3 cell lines that are driven by either FGFR 1, FGFR2, FGFR3 or FGFR4. The top table shows the IC50 of the different inhibitors against each of the different FGFR family members, as well as TYRA-300's high potency for FGFR3, which had an IC50 of around 1.8 nanomoles. The bottom table shows the fold selectivity for the other FGFRs relative FGFRs over FGFR3. You can see that all of the approved agents have similar or identical FGFR1, 2, and 3 activity, even though FGFR3 is the target in urothelial cancer. In some instances you can see that there's some separation for FGFR4, like with pemigatinib and infigratinib. Importantly, TYRA-300, we see double-digit fold separation across all of the family members relative to FGFR3. I'll emphasize again that FGFR1 is associated with hyperphosphatemia. FGFR2 has been shown to cause dry mouth and stomatitis, keratitis, skin and nail toxicity. FGFR4 has been associated with dose limiting GI toxicity. That includes diarrhea and liver toxicity. Any efforts to create a more FGFR3 selective drug has the potential to hit the target harder and reduce toxicities that have been a challenge in this class of drugs. On the next slide, you can see that we have in vivo data that confirms TYRA-300 selectivity over FGFR1. In a preclinical rat experiment, we measured serum phosphate levels 24 hours after a single dose of either erdafitinib or TYRA-300. As you can see, there is a dose-dependent increase in serum phosphate after a single dose of erdafitinib, whereas we don't see an increase in serum phosphate with similar doses of TYRA-300. Here on the next slide, what we show is an in vivo model using the human UM-UC-14 bladder cancer model, which is driven by an S249C mutation, which is the most common mutation in bladder cancer. TYRA-300 has good antitumor activity with both a 9-milligram BID and an 18-milligram Q day dose. It's important to note that we are treating at a lower dose than with erdafitinib at 12.5 milligrams BID. We believe we're starting to expand the window of efficacy and safety against the approved agent in this preclinical model. On the next slide, as Todd mentioned, TYRA-300 was designed to be active against the gatekeeper mutation that arises in patients that are treated with an FGFR inhibitor. Here we're showing on the left-hand side an FGFR3-TACC3 fusion in a human bladder cancer cell line, RT112. All of the approved agents in TYRA-300 have low nanomolar IC50s against the wild type FGFR3 that you can see in the gray box. Importantly, when we CRISPR in a gatekeeper mutation, you can see that all of the other agents, except for TYRA-300, fall off several hundred, even 1,000-fold in activity. Lastly, on the next slide, we show that the potency of TYRA-300 against the gatekeeper mutation is reproduced in vivo. On this slide, you can see that both TYRA-300 and erdafitinib have good antitumor activity against the TACC3 fusion cell line on the left, which is the parental cell line. On the right-hand side, in the presence of the gatekeeper mutation, TYRA-300 maintains its antitumor activity, whereas erdafitinib is now ineffective. All this preclinical work has led us to the point now of bringing TYRA-300 into the clinic in our Phase I/II study, SURF301. We chose the name given that TYRA is a San Diego-based company that's near a lot of great surfing spots. The study also stands for Study in Untreated and Resistant FGFR3-positive Advanced Solid Tumors. On the next slide, you can see SURF301, which is an international multicenter open label Phase I/II study. The Phase I p ortion consists of two parts with the goal of determining the maximum tolerated dose and choosing the optimal Phase II dose for later development of TYRA-300. Part A above will enroll patients with any solid tumor regardless of FGFR3 mutation status, so that we can determine the MTD as quickly as possible. Part B below will enroll FGFR3-positive patients in multiple dose expansion cohorts to explore the inhibition of FGFR3 relative to the other family members. The design of the study is once we clear those where we believe we're starting to inhibit FGFR3 in Part A, we'll begin to enroll additional FGFR3-positive patients in backfill cohorts in Part B at the same time while we're dose escalating in Part A. This will give us multiple doses to evaluate the biomarker and efficacy endpoints to fulfill some of the guidance that FDA has outlined for Project Optimus. We believe that FGFR3 inhibition may not be dose limiting, and the maximum tolerated doses may actually be due to inhibition of other FGFRs such as FGFR1 or FGFR2. The design of the phase I is to help ensure that we're not necessarily choosing the maximum tolerated dose, but one that we believe most optimally balances efficacy against FGFR3 and tolerability by sparing FGFR1 and FGFR2. SURF-301 is currently open and enrolling adult patients with advanced urothelial carcinoma and other solid tumors with FGFR3 gene alterations. We're really pleased to report that the first doses in SURF-301 were administered at Macquarie University in New South Wales, Australia. As this is an international study, it's a real privilege to have many sites such as Peter MacCallum Cancer Centre, Memorial Sloan Kettering Cancer Center, the University of Washington, Cleveland Clinic, Institut Gustave Roussy, Dalhousie University, and Dana-Farber Cancer Institute working with us to advance the study. In summary, we're really excited to evaluate TYRA-300 in the clinic, and we're working hard with our sites to identify and enroll more patients so that we can deliver an important therapeutic option for patients with urothelial cancer. With that, I'll turn it back over to Todd for closing remarks. Thanks, Hiroomi. Before we open the call for questions, I wanna communicate the enthusiasm we have for our robust pipeline. We feel we have tremendous momentum heading into the end of this year and into 2023. We are now a clinical-stage company with the first oral FGFR3 selective agent to be evaluated at the clinic, uniquely positioned to capture an outsized opportunity of bladder cancer. We plan to be thoughtful about the way we read out data from our SURF-301 study, and we'll keep you updated on our plans as our data mature. Each of our other programs has the potential to address meaningful opportunities and were designed to be best-in-class therapies within their respective indications, including our FGFR1/2/3 inhibitor TYRA-200 and programs for Achondroplasia, FGFR4 and RET. We remain well capitalized with $263 million in cash at the end of Q3 2022. TYRA is in our strongest position yet as a company. We look forward to continue to innovate and target oncology with our purpose-built therapy. Operator, we're now ready for questions. Ladies and gentlemen, at this time, we'll begin the question-and-answer session. To ask a question, please press star and then one using a touch-tone telephone. To withdraw your questions, you may press star then two. If you are using a speakerphone, we do ask that you please pick up the handset prior to pressing the keys to ensure the best sound quality. Once again, that is star and then one to join the question queue. Our first question today comes from Tyler Van Buren from Cowen. Please go ahead with your question. Hey, guys. Good morning, and thanks very much for the presentation. ClinicalTrials.gov states that you're starting at a 10 mg once daily dose, I believe. Can you remind us how that compares to the 12.5 mg/kg dose used preclinically in xenograft models? Perhaps most importantly, to what extent will you be able to dose escalate in humans, and what dose level in humans do you think will be therapeutically active? Thanks, Tyler, for the question and a great question. I think it's important to highlight, you know, because we did compare directly with erdafitinib, the approved dose for erdafitinib, is actually less than 10 migs. For, for, you know, comparing directly here, you know, this is a reasonable starting dose, but certainly, we, you know, we expect, you know, to learn different information about, you know, exposure as we move through different animal models and the human being a unique one. I think we're gonna wait for the data, understand exposure, and as Hiroomi indicated, we'll continue to dose up. As we see exposures, that we think are relevant in terms of, having FGFR3 activity is when we'll start to expand. At this point, we're gonna wait to see the data, I think before we make any strong assumptions about which dose will ultimately be the optimum or recommended phase II dose. Okay. That's helpful. I wanted to ask on just a second topic, I guess. Efficacy in part B is fairly straightforward, I suppose, but what biomarkers will you be looking at specifically, and how should we interpret them as we think about the selection of the recommended phase II dose? Hiroomi, do you wanna take this question? Yeah, absolutely. As you may know, FGFR3 is actually quite challenging from a biomarker standpoint. We know, you know, what the biomarkers are for FGFR1 inhibition. For FGFR3, the, you know, there's literature to indicate with the FGFR3 monoclonal antibody that urinary MMP1 might actually be a good marker for FGFR3 activity. We're gonna look at both serum and urine biomarkers across a spectrum of platforms to see if not only MMP1, but other potential markers may be regulated in response to TYRA-300. In addition to that, we'll also be collecting serial ctDNA samples from both plasma and urine to look at changes in circulating tumor DNA to really help us understand at a much earlier time point whether or not we're having an anti-tumor effect. Then we're also looking at skin biopsies, where if you may know that in skin, FGFR1, 2, and 3 are being expressed in different parts of the skin. So these skin biopsies, by doing digital spatial profiling, we'll be able to actually determine when we're starting to inhibit FGFR3 relative to the other FGFRs in a dose-dependent fashion. We think that we have a robust biomarker strategy to really understand the biology here, as well as to optimize the dose relative to the toxicities. Okay, that's great. Thank you very much. Our next question comes from Geoff Meacham from Bank of America. Please go ahead with your question. Good morning, guys. This is Hao calling in for Geoff Meacham, thanks for the question. Obviously, congratulations on this important milestone. My first question is, you know, given the commercial erdafitinib, which is more a FGFR2, 3 inhibitor, do you see there's a need to block both FGFR2 and 3 to achieve anti-tumor activity in urothelial cancer? If you have any preclinical data to support that blocking FGFR3 only is sufficient. Hello? Hello. Can you hear me? Oh. Oh. Sorry. This is Todd. I can take this call, but I just want to start off by thanking Jonathan Rosenberg. I know he's going to need to run to the clinic, so want to go ahead and release him and thank him for his contributions. As we, you know. Yeah. Thank you, Jonathan. For the specific question about whether or not it's valuable to also block the other FGFR isoforms, I think the best data we can share there is what Hiroomi walked through today, and that is two well-validated bladder cancer cell lines, one the UM-UC-14 and the other the RT112. Both of which have been validated as FGFR3 driven cancer cell lines via CRISPR. As we look in our own preclinical models, it's clear that with an FGFR3 selective agent like TYRA-300, we get really good antitumor activity. That's compared, of course, to erdafitinib, which is a pan-FGFR. That's, I think, the strongest data we have that suggests that these really are driven by FGFR3 and it's the molecular alterations that are either fusions or the dimerizing mutations that are driving these cancers. Great. That's helpful. Just another quick question. It looks like the FGFR3 mutation in non-invasive blood cancer was much higher, like 70%, while in metastatic urothelial cancer was, you know, 20%. Any reason why the difference of percentage-wise, and also, you know, if you wanted to move into earlier stage of blood cancer, what would be the safety bar required to enable the moving into the early line of the bladder cancers? Yeah, two great questions. I think with the first question, you know, the best answer is it's not clearly known. I don't think there has been, you know, conclusive data, you know, to explain why that frequency potentially goes down. Of course, you can imagine that as tumors get more invasive, they may be acquiring additional mutations that help them advance. Ultimately, we know that the incidence of FGFR3 positive mutations in earlier stages of disease are quite high. As you talked about the bar here, you know, standard of care, you know, in MIBC, in the earliest stages of diseases, you know, is BCG installation. Which does come with side effects and a pretty high burden in terms of patients' visits to the urologist and really treatment costs in managing these patients over a very long time as they continue to recur. An agent that is potentially well-tolerated that can be taken, you know, daily as an oral medication, that could, you know, essentially spare the cost and burden of frequent appointments to urologists, but also, and most importantly, the costs ultimately of recurrence, cystectomies and metastatic disease, we think, you know, is really exciting and really important for patients. With a safe and tolerable treatment, you know, I think that that's really the bar. You know, improving the convenience for these patients, I think could make an agent, an FGFR3 selective agent like TYRA-300, you know, potentially an excellent treatment option for these patients. Great. Thank you. Congratulations again. Thank you. Our next question comes from Maury Raycroft from Jefferies. Please go ahead with your question. Hi, this is Kevin on for Maury. Congrats on the update, thanks for taking my questions. Just the first question, I guess, for Todd. You know, you mentioned that you spoke with the FDA on opening up earlier cohorts. Could you just clarify whether that would be for non-muscle invasive or also for muscle invasive? Then, you know, you talked about adequately establishing the safety and efficacy. Do you have any specifics on when that could be? Could that be after the recommended phase II dose? Did you discuss a specific efficacy bar as well as safety? Yeah. Great questions, Maury. I'll hand it over to Hiroomi to answer this question and specifically related to, you know, correspondences with the FDA about MIBC. Yep. Thanks, Todd. I think what's important, is that the risk benefit for metastatic disease, is very different, than it is for the earlier settings. FDA was clear with us that they wanted to see, some initial efficacy data in metastatic patients before we moved into recurrent non-muscle invasive bladder cancer. Really it's around, establishing that we have a drug that has antitumor activity that's well-tolerated before going into earlier lines. In terms of your second question, remind me what that was. Just if you were, you know, if it was muscle invasive, as well as non-muscle invasive. you know. So- Yeah. Sorry. Go ahead. Yep. We do have some thoughts around muscle-invasive bladder cancer, whether or not it's a potential window of opportunity study. You know, we haven't. Those plans haven't fully matured, but we think that there are opportunities for a well-tolerated drug to be used in settings where we can really do some important biologic work as well as dose ranging in these earlier lines of bladder cancer. Okay, great. Thanks. Just a follow-up on, you know, enrolling the study with sort of the current landscape around genetic testing capabilities. You know, do you have any line of sight in terms of what you expect the pace of enrollment to be, you know, at MSK and then at other sites as well? We've specifically gone to institutions that do a lot of NGS testing. You know, that was very purposeful to be sure that these sites were able to identify potential candidates for the study. In addition to that, we are using liquid biopsy to help screen patients. We believe that particularly in the metastatic resistant population, that rather than putting patients through a tumor biopsy, that a liquid biopsy will really help in terms of identifying these patients much more quickly. That's, you know, part of our strategy is again to go to sites that do this routinely, but also to provide an additional testing mechanism that broadens the patient pool. Great. Thanks, Hiroomi, I'll jump back in the queue. Our next question comes from Mitchell Kapoor from H.C. Wainwright. Please go ahead with your question. Hi. Thank you for taking our questions. just wanted to ask, you know, how could you potentially pursue a tumor-agnostic strategy versus single indications? How could those strategies look different if you see activity, in one or more? All right. Thanks, Mitchell. I think, one thing to highlight that in our phase I/II design, we do have a cohort for tumor-agnostic patients. We do rely on next generation sequencing that is starting, you know, increasingly occurring across multiple sites and ultimately multiple indications to help recruit into that study. We have seen some initial data from erdafitinib, for example, that was published earlier this year in a tumor-agnostic setting. So we would follow a similar path within that cohort to evaluate patients, not based off of their tumor types, but based off of FGFR3 positive disease using some of the standard activating mutations and fusions that are seen in bladder cancer and have been validated there. Okay, great. Thank you. You know, what kind of learnings can you take from the development of other therapies that address gatekeeper mutations such as osimertinib? Is there anything that, you know, helps guide your thinking of clinical development? Yeah, it's really a great question. We shared some information on other targets and agents in the material today. We do that because we think that data are becoming increasingly clear that agents that address acquired resistance have the potential to improve or extend progression-free survival. I think one way to help validate this is it's important to show up front that when you have a, you know, gatekeeper mutation, for example, in a patient that is starting to recur, the ability to bring some of those patients back into a response or at least stabilize their disease provides strong evidence that moving earlier in line has the potential in a naive patient population to move the progression-free survival even further out by essentially preventing that acquired resistance when we think it would occur. We take that approach across our indications in thinking about addressing acquired resistance and the benefit that next-generation inhibitors might have for extending progression-free survival. Great. Thank you so much, Todd. Our next question comes from Jennifer Kim from Cantor Fitzgerald. Please go ahead with your question. Hey, team. Congrats on entering the clinic and for the helpful presentation. I just have a few questions here. The first is more of a competitive question. You're a bit ahead in development of another FGFR3 selective inhibitor from Lilly, I think they're entering the clinic maybe before the end of this year. Are there any key differences you'd highlight for your selective asset or differences in the way you're approaching your clinical or development strategy? For example, I know they're including a PD-1 combo arm already, I'm wondering does that change the timing of when you could start exploring a combination? Thanks. Yeah. Hi, Jennifer. Thanks for the very thoughtful question. I think it's important to start off by saying that, you know, we encourage drug developers' next generation therapies for patients. I think this is more options for patients, better agents that can improve outcomes, is really what our collective goal is here. It is good, we think, to obviously see other activity in this space for the benefit of patients. It's hard, you know, today as where we stand to compare, you know, our agents relative to theirs, as there's pretty limited data out there on Lilly's agent. Whereas, obviously with some of the approved or later-stage development assets, we could do some of the more direct comparisons. I won't comment too much there. On clinical study design, I think as Hiroomi indicated, we really highlighted the phase I portion here, which is to move as quickly as possible to an optimum recommended phase II dose, understand the MTD. We will and intend to move, you know, pretty quickly as well, in exploring potential combinations and other ways that we can really progress TYRA-300 in the treatment paradigm here, coming out of that initial phase I readout. Okay. That's helpful. Hiroomi, did you wanna add? One more question. Oh, sorry. Yeah. Hiroomi, did you wanna add anything there? Yep. Yep, sure. I think that, you know, we wanted to provide ourselves with some optionality as well. You know, we have the potential to, as soon as we have an optimal phase I dose, we can very easily amend the protocol to add a PD-1 cohort. At the same time, we may wanna go to a broader strategy of combining the different PD-1s, and really, you know, help us understand sort of the landscape, and, you know, help us with potential business development. I think that, you know, there are a lot of things that we want to be able to do. We haven't made them explicit yet as, you know, as we're still relatively early. I think that, you know, PD-1 combinations as well as combinations with other, novel ADCs, you know, is really part of our development plan. Okay. Then one quick question. Have you said that the total number of clinical sites you anticipate for the trial? for phase I. Yep, for phase I, I believe. Go ahead. ... we'll have a total of about 18 sites across the U.S., Australia, France, and Spain. For phase II, we'll, you know, we're in the process of doing the feasibility. Okay. All right. Very helpful. Thanks again. Ladies and gentlemen, with that, we'll be concluding today's question-and-answer session. I'd like to turn the floor back over to Todd Harris for any closing remarks. All right. Thank you again for joining us on the call today. We're extremely excited about our recent progress. We look forward to harnessing our momentum and advancing our entire pipeline into the new year. Operator, ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect. Goodbye. Ladies and gentlemen, with that, we'll conclude today's conference call and presentation. We do thank you for joining. You may now disconnect your lines.