Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Tyra Biosciences Investor Conference Call. As a reminder, this conference is being recorded. Now I'd like to turn the call over to Amy Conrad from Tyra Biosciences. Please proceed. Thank you, operator. Good morning, everyone, and thank you for joining us. With me today from Tyra Biosciences are Todd Harris, Chief Executive Officer, and Doug Warner, Chief Medical Officer. We are also excited to be joined by Gary Steinberg, Professor of Urology, Department of Urology at Rush University Medical Center. Dr. Steinberg will be available for questions during the Q&A period of the call. For those of you participating via conference call, the slides are available via webcast and can also be accessed by going to the For Investors page of our website. Before we begin, I would like to remind you that on today's call, we will be making 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 provisions 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 risks and uncertainties associated with Tyra's business, including those discussed in our filings with the SEC. In addition, 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. Now I'll turn the call over to Todd Harris. Todd Harris? Thank you, Amy Conrad. Welcome, everyone, and thank you for joining us this morning. Today is an important day for Tyra Biosciences and one that we've been working towards for the last several years. From the beginning, we had a clear and purposeful focus on FGFR biology, which offers us a wealth of opportunity in targeted oncology and genetically defined conditions. In a short amount of time, we've built a differentiated pipeline with multiple clinical-stage programs in areas of high unmet medical need. I'm pleased to share today that we have achieved interim clinical proof of concept with our lead program, TYRA-300, from our SURF301 study in patients with metastatic urothelial cancer or mUC. Before we dive in, I want to take a moment to thank the patients and their families for participating in our study. We understand that metastatic urothelial cancer is a debilitating cancer with many challenges on the patient journey. We sincerely appreciate the willingness to participate in our study and help us bring TYRA-300 one step closer to patients who need it. We also want to thank the principal investigators, study sites, and all those responsible for getting us to this moment today. I'm pleased to report that the data Ben Tran is sharing at the Triple Meeting today are exactly what we were expecting to see with TYRA-300. In terms of efficacy, we benchmarked our clinical activity against the erdafitinib label in FGFR3+ mUC patients at active dose levels and reported a 54.5% clinical activity rate, with six out of 11 confirmed partial responses at 90 mg QD or greater. On PK/PD, we achieved a dose-dependent effect with anti-tumor activity observed in FGFR3+ mUC at 90 mgs QD or greater. And on safety, we wanted to show favorable safety profile with improved tolerability in FGFR1, FGFR2, FGFR4 driven toxicities compared to pan-FGFR inhibitors. So far, we are pleased with what we see, and TYRA-300 is generally well-tolerated with infrequent FGFR 2 and FGFR1- associated toxicities. With that, Doug Warner will take you through the interim clinical results, and I'll come back to provide commentary on what's next for TYRA-300 in all indications we are pursuing, including mUC, but also NMIBC and achondroplasia, where we see great opportunity based on the triple meeting data. Doug Warner? Thank you, Todd Harris. I'm going to start my remarks by providing an overview of the FGFR3 target and its role in bladder cancer. FGFR3 oncogenic alterations are common in bladder cancer. They consist of mutations which cause dimerization of the receptor and fusions on the kinase domain. Both of these alterations cause the FGFR3 receptor to be constitutively active, independent of ligand. In mUC, 10%-20% of patients are FGFR3 +. Oral erdafitinib is a pan-FGFR inhibitor approved in this setting and has a 35.3% overall response rate. Infigratinib and pemigatinib are not approved in this setting, but were tested and showed limited overall response. In earlier stage disease, non-muscle invasive bladder cancer, FGFR positivity is a lot higher, and oral erdafitinib and infigratinib have been tested in intermediate risk and high risk and showed high complete response rates. Unfortunately, the toxicity associated with the pan-FGFR inhibitors limits their use and has a great deal of impact on patient quality of life. Pan-FGFR inhibition is associated with key on-target toxicities. Here we see first, the FGFR2 related toxicity. It consists of high rates of nail disorders, consisting of nail infection and nail loss, stomatitis or mouth ulcers, PPE, also known as hand-foot syndrome, which is a painful swelling and blistering of the hands and feet, and a high rate, almost 20%, of central serous retinopathy. FGFR1 related hyperphosphatemia occurs in almost 80% of patients receiving pan-FGFR inhibitors and often results in the use of phosphate binders. Other AEs that are common in pan-FGFR inhibitors include diarrhea, ALT, AST increase, and dry skin. As mentioned, these on-target toxicities result in high rates of dose modification. Dose interruptions occur in 72% of patients on erdafitinib, and dose reductions occur in 69% of patients on erdafitinib, with a discontinuation rate of 14%. TYRA-300 is a potential first-in-class, highly selective FGFR3 inhibitor that was designed to avoid these pan-FGFR toxicities. Here, we see that TYRA-300 has high potency for the FGFR3 receptor, but orders of magnitude less potency for FGFR1, FGFR2, and FGFR4. Our phase I study explored QD dosing in a dose escalation phase that enrolled all solid tumor types, both FGFR3 + and FGFR-, and a dose expansion phase, which enrolled solid tumors with a focus on mUC and enrolled FGFR3+ patients only. We dose escalated up to 120 QD and then expanded up to 90 mg dosing. The study population overall was older and heavily pretreated, with a median age of 66, about even numbers of mutations and fusions, and 76% of patients with mUC had 3 or more lines of prior therapy. Preliminary data suggests TYRA-300 is well tolerated, with the vast majority of treatment-related adverse events low Grade. The most common treatment-related adverse events were low-Grade ALT increase, diarrhea, dry mouth, and AST increase. There was only one DLT, and that occurred at the 90 mg dose. It was a Grade 3 diarrhea. There was only one drug-related discontinuation that was also at the 90 mg dose due to a Grade 3 ALT elevation. There were no drug-related discontinuations or reductions at the 60 mg or below dose. There were four related SAEs, and there were no Grade 4 or higher related SAEs, and in fact, there were no Grade 4 or higher AEs overall in the study. Minimal changes in phosphate levels occurred at the dose of 90 mgs and below, and only one patient required a phosphate binder that was at the 90 mg dose. As we see on the left, exposure at doses of 90 mgs exceeded the FGFR3 IC90 target coverage. We also see that at this exposure, it was well below the IC50 of FGFR1, FGFR4, and FGFR2. On the right, we see that exposure at doses greater than 40 mg was higher than dose proportional. Here we see an elegant translation of the preclinical model onto the clinical data from the SURF301 study. We see that the anti-tumor activity associated exposure from the murine model is plotted against the clinical data from the study, and at doses of 90 mgs or above, the exposure is greater than the exposure seen in the mouse model. Here we see the waterfall plot, radiographic tumor response assessment in all evaluable patients. The evaluable population excluded patients who didn't have measurable disease or didn't reach the first scan time point. First off, we see that the preponderance of responses occurred in FGFR3+ mUC. Specifically, in mUC, all of the partial responses occurred at doses of 90 mgs or above. In the light gray, you see there was one partial response in an FGFR fusion+ head and neck cancer patient. Looking specifically at the doses of 90 mgs or above, we see there was a 100% disease control rate in this population. There were six confirmed PRs at 90 mg dosing and above. A population of 11 patients, there were five confirmed PRs at 90 mgs out of 10 patients, and one confirmed PR at 120 mgs out of the single patient who was dosed with mUC at this level. Here we see the swimmer plot depicting time on treatment for the target population of FGFR3+ mUC. There's a clear dose response in terms of time on treatment and confirmed partial responses. We also see at the 90 mg dose, there are two unconfirmed partial responses, and three patients remain on treatment with confirmed partial responses. At 90 mgs, we saw a clear improved tolerability compared to erdafitinib. When we look at FGFR-driven toxicity, we see low- single-digit toxicity for many of these AEs. There was one case of Grade 3 stomatitis, which lasted less than seven days and did not result in dose interruption, and one case of central serous retinopathy in a patient who came on treatment with vitreal detachment. There were low rates of hyperphosphatemia and lower rates of diarrhea compared to erdafitinib. ALT and AST increases were similar to erdafitinib. Here we see the spider plot showing radiographic regression, where all patients saw radiographic regression at the first scan time point. I want to focus in on two of these patients. The first patient is an 84 year-old woman with an FGFR3 mutation. Patient had received four prior lines of therapy, including enfortumab and an anti-PD-1. Patient had a target lesion in the lung, and here you can see a remarkable response at the confirmatory scan. The patient remains on treatment at eleven months. Here's the case of a 64-year-old man with a fusion, who had two prior lines of therapy and target lesions in the lung and lymph nodes. Here you can see one of the lung lesions with complete resolution in the lesion at the confirmatory scan. This patient remains on treatment at 11 months. So the interim proof of concept has been established with TYRA-300 in mUC. The preliminary data from SURF301 suggests TYRA-300 to be well tolerated, with infrequent FGFR2 and FGFR1-associated toxicities. TYRA-300 plasma concentrations indicate adequate target coverage at the dose of 90 mgs daily and above, and further pharmacokinetic characterization is ongoing. Preliminary antitumor activity of TYRA-300 in heavily pretreated patients is very encouraging, especially at doses at 90 mgs daily. Phase I is ongoing, and the MTD has not yet been reached, and optimal dose has not yet been determined. The compelling emerging data warrants continued development in mUC with the prioritization of QD dosing. And with these remarks, I want to hand the call back over to Todd Harris. Thanks, Doug Warner. We are really excited about the future at Tyra and the many opportunities we have to deliver benefit to patients with TYRA-300. Before we take your questions, I want to walk you through each development opportunity in mUC, NMIBC, and achondroplasia, and our goals for each indication. First off, I want to recognize the important pioneering and validating work that others have achieved in conditions driven by FGFR3. J&J has demonstrated with erdafitinib, the potential efficacy that can be achieved with FGFR3 inhibition in both mUC and NMIBC. BridgeBio has shown that FGFR3 inhibition with infigratinib has, at a low dose, the ability to have a meaningful impact on AHV. Because of this precedent work, we can potentially read through our initial SURF301 results to opportunities that we might pursue, not just in mUC, but in NMIBC and ACH. This includes identifying optimal dose ranges in NMIBC and ACH that we expect to be lower than the 90 mg mUC dose we've been highlighting today. Let me start with NMIBC. Bladder cancer is a very large attractive market, with approximately 700,000 patients living with bladder cancer in the U.S., and an overall addressable population that we anticipate as around 163,000. Nearly half of these have FGFR3-driven disease, and in the largest segment, intermediate risk NMIBC, the FGFR3 positivity is very high, at 60%-80%. We are planning to target intermediate risk NMIBC patients first in our development. As you might know, proof of concept was established with erdafitinib in the THOR-2 trial in intermediate risk NMIBC. It showed great efficacy with a CR rate of 83%, but the toxicities demonstrated caused most patients to discontinue from the study. Due to toxicities, J&J ultimately stopped developing erdafitinib as an oral agent in the NMIBC and have prioritized local delivery of erdafitinib with their TARIS platform as TAR-210. We believe that we have a great opportunity with TYRA-300 in NMIBC based on the interim clinical results, including safety and tolerability at lower doses, which I'll show on the next slide. Here we are showing our safety tables at lower doses. We see infrequent FGFR-related toxicities, and importantly, at doses 60 mg or lower in a late-line cancer population, in terms of TRAEs, we saw no Grade 3 and higher events and no hyperphosphatemia driven by FGFR1, which was a problem in the THOR-2 study. Like erdafitinib, which explored a dose 2/3 lower than mUC in the THOR-2 study, we plan to explore doses around 60 mg of TYRA-300 as we get into NMIBC. For achondroplasia, we'll be looking at doses even lower than that. What's up next? We are planning to continue dose optimization with TYRA-300 in the SURF301 study. We plan to submit a phase II IND in intermediate risk NMIBC, and we are preparing to initiate a phase II study in achondroplasia. We truly believe we have a jewel in TYRA-300 with a rare opportunity to solve important unmet needs in three separate, large, and attractive markets. We look forward to the opportunity to push the development ahead. With that, we'll turn it over to the operator to facilitate questions. Thank you. If you'd like to ask a question, please press star one, one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. In the interest of time, we ask that you please limit yourself to one question and re-queue if you'd like to ask a follow-up. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open. Great. Thanks very much. Good morning, guys, and congratulations on the fantastic data presentation. So just to confirm, at the doses below 60 mg, you saw, I guess, no FGFR 1 and FGFR2 -related toxicity? And how are you thinking about picking between the achondroplasia and the NMIBC dose as you move forward? And maybe Dr. Gary Steinberg, you could just comment on if you believe the safety profile is good enough to get broad adoption by urologists in NMIBC. Yeah, thanks, Tyler Van Buren. I'll take the first one. Yeah, we saw no hyperphosphatemia, and as we highlighted on this page, you know, really low rates of the key associated toxins that we saw, maybe at higher doses. So the real reduction in ALT we find to be quite encouraging. I think it'd be great for, when Dr. Gary Steinberg speaks, to speak to his view of this profile relative to, you know, what, what he saw or his experience with erdafitinib. I think there was one other piece of your question, though. You asked about the toxicities, and then, was it which dose are we planning to explore? ... Exactly, between ACH and NIMBC, how do you choose two different doses if it looks so clean below 60 mg? Yeah, so around 60 mg is where we're gonna explore, and obviously, we wanna do dose optimization for optimal safety, with still, yeah, great efficacy. When we look at achondroplasia, we actually anticipate that FGFR3 may be the top driver of not wanting to dose up anymore. And so we generally are looking at a dose that we've said about half the oncology dose. So consider a 40 mg-45 mg adult dose. That would go no higher than that due to what we anticipate being really strong FGFR3 activity that should be hitting the target the right way. We'll be exploring doses there and below ultimately. And then maybe I can hand over to Dr. Gary Steinberg on the question you asked for him. Thank you, and thank you for an excellent presentation. There's no question that the dosage that you more likely than not need for non-muscle invasive disease can be, and most likely will be, significantly lower than the dose you need for metastatic urothelial cancer. The amount of disease burden is significantly lower, and certainly we saw in the THOR-2 trial with oral erdafitinib, that we were using a significantly lower dose than is prescribed in the metastatic setting. There's no question that patients with non-muscle invasive bladder cancer, they clearly, if they're going to be taking this medication long term, clearly desire and need a acceptable toxicity, and I think that the data here clearly demonstrates that. More importantly, patients can have dose reductions or dose holidays. One of the things that we saw in the THOR-2 data that was presented at ESMO in 2023 is that even though patients did not take oral erdafitinib for more than four or five months, I think that the maximum was up to seven months, there was still a significant decrease in events in patients that were on the erdafitinib when you follow them out to 12 months. So it's unclear that we need to treat patients forever with this drug. Certainly, they may need it intermittently. But there's no question that on one hand, we want a drug that's safe and tolerable, and clearly the non-muscle invasive patient population is different than the metastatic. But patients do not want recurrences. If they know that this drug is gonna prevent them from having to go to the operating room and prevent them from having recurrences and gonna keep them disease free, they're gonna be more than willing to accept some minor side effects, such as we see when patients take statins or antihypertensives or medications for diabetes and so forth. Clearly, I think that the data to date that has been presented at the 60 mg dosage demonstrates very acceptable overall toxicity. Clearly, in the erdafitinib trial, the toxicity was very significant, and most patients were not able to tolerate the drug. I think this is a major move forward. Thank you. Our next question comes from Chris Raymond with Piper Sandler. Your line is open. Yeah, thanks and congrats from us on the data as well. Just maybe I wanna make sure I understand the definition of hyperphosph that you guys sort of mentioned. When looking at the poster, you know, I think you were using a threshold of 2 mM per L, but the definition, you know, in the broader presentation is greater than 7 mgs per deciliter. Just can you maybe sort of talk a little bit about the difference in the language there that you sort of describe and just confirm, you know, no hyperphosphatemia, I guess, incidents in the trial? Sure. So the grading of the hyperphosphatemia AE is based on CTCAE criteria, and that's based on the intervention. So Grade 1 is no intervention, Grade 2 is a non-invasive intervention, meaning phosphate binding agents are used. And so in our trial, there were two cases of hyperphosphatemia at the 90 mg dose, with one case being Grade 1 and the other being Grade 2, with that patient who had a phosphate binder at the 90 mg dose. In general, you know, if you look at the pan-FGFR inhibitors, their labels recommend initiating phosphate binder treatment at a level of seven or above. So sometimes that level is used as sort of an indicator that treatment with a phosphate binder is required. But once again, the CTCAE criteria is based on the type of intervention itself. Great. Thank you. Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is open. Hi, I'll add my congrats on the update, and thanks for taking my question. Just wondering what else you need to do in terms of enrollment and dose optimization, including additional work to validate the safety profile you're seeing before meeting with FDA to get alignment to start a study in NMIBC? Can you talk more about timelines for these next steps and whether you'd do another data cut from the SURF301 study? Yeah. Thanks, Maury Raycroft. I'll take this one. I think at the... We are still, you know, we are still dose optimizing. I think the data we're presenting here gives us a lot of encouragement about the 90 mg dose and its performance. Of course, you know, Project Optimus. FDA really does like sponsors to be able to bring two unique sets of doses with unique PK to evaluate, you know, an optimal dose. So we wanna do the work to fill Project Optimus and round this out as we move into phase II. So there will be still some efforts to ensure that we fulfill that criteria and then move forward with the recommended dose. But what we highlighted here is we are prioritizing QD dosing, and what we're seeing here is, you know, is exactly what we would hope to see. So, on the question of NMIBC, the key gating criteria for us from FDA is they wanted to see some proof-of-concept data in this patient population for us to be able to open up a study there. And I think we feel based off of the strength of the data we're presenting today, that we have that data package, so the next step for us is to leverage this to submit an IND for NMIBC. Did I get all of your questions? Yeah, I think so. I don't know if you're gonna do another data cut from this study or not, and if you're talking about when that could happen. Yeah, we don't. Yeah, we're not going into any additional data cuts from here. I think we're gonna backfill doses and continue to move this forward. Of course, as we get closer to, you know, a next mature data set, we can guide towards that, but we're not gonna set any expectations just yet on when that will be. Understood. Okay, thanks for taking my questions. Thank you. Our next question comes from Matthew Biegler with Oppenheimer. Your line is open. Hey, guys. Congrats from us as well, and thanks for the call. I wanted to also ask about safety, particularly those two Grade 3 ALT elevations. You know, is that idiosyncratic, or is that something you'd expect? I guess I don't know if FGFR3 is expressed in the hepatocytes, but also, how does that compare to erdafitinib's label? And happy to hear from Dr. Gary Steinberg, if he also has any commentary on that. Thanks. Thanks, Matthew Biegler. I'll do a quick answer, and then I think get Dr. Gary Steinberg view. But yeah, as Doug Warner had mentioned on the call today, you know, similar rates, if you look at erdafitinib. If you look at the other pan-FGFR inhibitors, they're actually pretty similar rates. And that's independent of whether those are FGFR4-sparing, like infigratinib and pemigatinib, versus, well, futibatinib and erdafitinib that do hit FGFR4. So I think what we're seeing is opening up some questions we wanna, you know, look into a little bit further. We've talked about our TYRA-430 program, where we highlighted that hepatocytes and hepatocellular carcinoma have high expression of FGFR3 or FGFR4 and are involved in this classic FGF19 pathway. That's certainly been linked with the FGFR4 inhibitors to, you know, some evidence of ALT, AST, diarrhea. So that's certainly something we'll follow up to understand, is this a, you know, is this a phenomenon from a general TKI, you know, you tend to see this? Is this something that's actually related to on-target activity? Those are important questions for us to follow up on. We're certainly encouraged that the rate isn't, you know, isn't different than what the other pan-FGFRs have seen. And I think maybe I'll hand it over to Dr. Gary Steinberg to talk about management of this and, you know, how big of a impact it would be in a metastatic population. Yes, and that's an excellent question, and again, I think we have to differentiate between laboratory values and clinical symptoms, but there's no question that the medical oncologists in the world have done a tremendous job in figuring out ways to mitigate and manage side effects of treatment. The greatest case in point is the checkpoint inhibitors. I mean, we're giving checkpoint inhibitors to multiple patients with multiple diseases, and we truly begin to understand what the side effects are, and more importantly, how to mitigate them, recognize them, and treat them promptly. And so I think that a treatment strategy for these AST or ALT elevations and the diarrhea will be readily available and will be a part of the algorithm of how to manage these. And I don't suspect that this will be a big problem. Clearly, the nails and the phosphate and the skin and the eye changes are much more difficult to manage and pretty much every patient that receives oral erdafitinib has these side effects. And we're clearly not seeing that with the 60 mg dose and even the 90 mg dose with TYRA-300. So I don't think it's going to be a big problem. Certainly, during the investigation, making sure we record all the AEs and come up with the algorithms to manage them, and I suspect that it should be pretty straightforward and not anything that would preclude patients from being able to receive medications. They may, you know, need to take a medication holiday for a couple of weeks or be intermittently treated, but I don't think it's going to be a major concern, especially when you look at the profile and compare it to erdafitinib. Awesome. Thanks again. Thank you. That's all the time we have for questions. I'd like to turn the call back over to Todd Harris for closing remarks. All right. Thank you, and just wanna thank everyone on the call today, and obviously, a great. You know, it's been a lot of years in the making. We couldn't be more excited about the profile that we're seeing. We really do have a jewel of an asset here, and we're excited now to move development forward, three parallel paths in mUC, NMIBC, and achondroplasia. So I look forward to engaging with this group as we continue to do that. Thank you, everyone. Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect. Goodbye.