Tyra Biosciences, Inc. (TYRA) May 13, 2026 Conference Transcript

Well, good morning. Thank you all for joining us here on our second day of the annual Bank of America Healthcare Conference in very toasty Las Vegas. I'm very pleased to be up here this morning with Todd Harris, Chief Executive Officer of TIRA Biosciences. Todd's going to run us through a few slides and then we'll open up to Q&A. So, Todd. Thanks, Jason.

It's great to be here. Thanks for having us. So I will be making some forward-looking statements today. Excited to highlight just up front here what we talk about when we talk about Tyra and our DABO 3x3 strategy. It's a very exciting year for us. It's a very exciting few years coming up for us. We have three potential blockbuster indications going into late stage development with our lead drug dabogratinib, a drug that has been validated in a phase one study and a late line metastatic as being a highly selective, very well tolerated FGFR3 selective inhibitor. It's touched over 100 patients today. And in the three indications that we're talking about, these are validated indications where FGFR3 inhibition has already demonstrated very meaningful outcomes, but where the current drugs by inhibiting other isoforms have run into significant toxicity challenges. It's where dabogratinib can truly stand apart. And to just highlight these indications, and they're quite compelling. In urethelial carcinoma, there's about 80,000 new patients a year. there's 700,000 patients worldwide with bladder cancer. FGFR3 mutations, and they're very specific ones, drive nearly half of these. But in the intermediate risk setting, low grade, and in the low grade upper tract setting, 75, 70, 80, 85% rates of FGFR3 positivity. So this is where the disease is really driving or where the gene target is really driving the disease. And it's exactly the gene target that we hit. These are really large opportunities, and we'll talk about it. In addition, FGFR3 is the driver alteration, the overexpression of FGFR3 that drives achondroplasia and several other skeletal conditions. Combined, these represent really meaningful opportunities to change the game for patients and to change patient care. We are, in many instances, the first in class and the potential best-in-class treatment option that can be delivered here. so let's actually start with what would be the biggest opportunity for us it's the intermediate risk nmibc indication and just to highlight the scale of this yeah you know we're talking about 35,000 new patients a year that are fgfr3 positive that could be addressed this is actually really comparable size of the market that a very successful drug called ostomertinib or Tigriso targets. Their EGFR positive lung cancer, there's about 33,000 new patients a year in the U.S. The average treatment duration of that drug is about 23 months. The average treatment duration we anticipate for dabogratinib is also going to be about two years. That drug, Tigriso-osomertinib, is about a $7 billion drug, and it's truly changed the game for EGFR positive lung cancer patients. That's the type of opportunity we're talking about here when we talk about the intermediate risk and MIBC. And let me just highlight a little bit more about why. And to do so, I really want to focus on the patient journey. And I'm going to ask the audience and those listening to go through an exercise with me. I want you to imagine 30, 40 years from now, you wake up one morning and you see blood in your urine. That's the first diagnosis of a potential bladder cancer. Now, you're going to call up your primary care doctor. They're going to tell you to get to your urologist. You're going to look up your urologist and realize, okay, they're probably over 30 minutes away from my house. You're going to schedule an appointment and you're going to show up in the office. And when you show up in the office, the diagnosis will look like this. You're going to be asked to lay out on a table. You might have a young nurse put this cystoscope up through your urethra after a little bit of numbing cream. And then while you're there live, the physician's going to look around and see the bladder cancer lesions and give you that diagnosis. Now you go home at that point, and it's pretty daunting. You look up, you see that survival rates if you're in the metastatic setting can be very poor. You see that if you're muscle invasive or even high risk, you may lose your bladder. And you see that in the intermediate risk setting, you are not necessarily going to lose your bladder, but the recurrence and the frequency of procedures can be quite intense. Obviously, you're hoping for the best case. The physician's going to go ahead and schedule you for a treatment to remove the tumors via turbot. You're going to come back two weeks later. You're going to lay out on the table, fall asleep. And when you wake up, the physician will have used one of these devices to selectively cut out with a hot wire each of your tumors, collect them. And at that stage, we still don't know necessarily what grade you are. The physician's going to send that out for pathology, tell you to go home rest and give you a call maybe a week or two later so in a great scenario you're going to get the news from the physician good news your intermediate risk that means you have a low risk of progression the challenge with your disease is that you may need frequent repeat procedures if you continue to recur it's at that setting that we hope to really change the game for the patient today all you're offered is a wait and see and a repeat surgical procedure or if you want to tolerate it you could be invited to come back once a week for six weeks once a month thereafter to get catheterized by that young nurse and to have chemo pushed into your bladder and to be asked to sit there for hours on end potentially trying to hold it in and then do that week after week after week with potentially even modest results but a huge burden on the patient for going in. And actually the scarring and the end result on the bladder itself, this can lead to just fibrosis and a significant deterioration of the bladder. Now, in today's setting, there are new treatments coming. Now, all of these treatments involve urethral violation. So STURY just got approved. This would be a once a week push chemo gel instead of chemo into the bladder. CG Oncology is looking to advance crestomogene. This would be a once a week pushing of viral vectors through a catheter into the bladder, potentially quarterly thereafter, maybe re-induction with once a week for six weeks as well. Or J&J, which is pursuing the TAR210 pretzel, which involves inserting and removing every three months a pretzel that stays with you every minute of every day. And it's something you feel. It's something that create urgency, UTIs and other challenges. If we are successful, one day a physician will be able to say, after your TURBIT diagnosis and low-grade diagnosis, I could drop ship you a drug, just take a pill a day, and we'll just monitor you over time. But this has the potential to reduce your recurrence. So hopefully I've been able to articulate why what we're doing could mean so much for changing standard of care for patients. Now, the reason we believe and we benefit immensely from some of the leading work that J&J did with ertifitinib is that ertifitinib provided at a lower dose showed a great CR rate in a study that looked at marked lesions in the intermediate setting 89 percent and for any patient that could stay on drug the durability was 100 percent which is remarkable but mechanistically actually makes sense once the tumor has been reduced as long as you stay on that drug you put daily pressure to keep those lesions from growing back now the challenge with this drug was the tolerability, and it was the tolerability due to the FGFR1 and 2 associated tox, things like hyperphosphatemia, eye disorders, nail disorders, mouth sores. That led to dose reduction in 61% of patients. Despite that, even with dose reduction, you saw this good activity. So J&J put this into the pretzel to get local delivery. That reduced the systemic tox, which is a great outcome. They got to an 81% three-month CR, so they were able to get to similar levels of efficacy and they've advanced this now into their moonrise study, their phase three. But when we look at what it looks like to have some of these intravesical therapies or even the pretzel place in the bladder, you can see that these are still associated with significant local AEs, things like 48% frequency or 44% UTI or the need to drink 1,500 milliliters of water or the issues with the urine becoming a biohazard after these events. So these are certainly not a walk in the park. We are in a current study and we updated our guidance today to highlight that we're going to read out in August an initial data set here where we're looking at two doses, 50 and 60 milligrams. These are the doses that we believe correspond in their AUC coverage to that efficacious dose that Ertafitin abused of six milligrams in the Thor2 study. We'll be reading out at least 10 patients of efficacy at each dose and quite a few more patients that have been on the drug for safety. We've enrolled well over 20 patients to date, and we continue to enroll pretty robustly. So come August, we anticipate that we'll have at least 10 to 15 efficacy readouts. That's three months CR, as well as a detailed update on safety for likely well over 30 patients in this study. So a really important data readout that's coming. This is going to be the determination of a go, potential no-go to phase three. If we need to test another dose, we can. So we can either move the dose up or down at that stage if we feel like we're not quite getting there. And the mark we've set for us is really hitting a 70% CR rate or better with the type of tolerability that we saw at these lower doses in our metastatic setting. Now, the unmet need here is truly procedural burden and surgical burden. It's really only an oral option that can address that. The Thor2 data sets the precedent with exceptional durability of 100% and that daily pressure on the tumor. With our SURF 302 study, we want to hit that 70% CR8 or better. We want to repeat the safety signal that we saw in 22 patients treated at either 40 or 60 milligrams in our metastatic setting. To us, that would be a huge success and a go decision for phase three. A lot of investors ask us, why is 70% enough? One important thing to keep in mind is this is a window of opportunity signal-seeking We intend to move into a phase three in an adjuvant setting where we're not going to be looking at CRA. We're going to be looking at disease-free survival. The expected disease-free survival at two years by doing nothing, which is often standard of care today, is about 60%. You can have about 40% of patients recur. We anticipate with a compelling hazard ratio, getting to a 78% disease-free survival or better would be an exceptional outcome. And really the minimum bar here is all we would need to show is that for these patients that have been able to stay on drug for two years, that we've reduced the risk by 45%. That's a 45% 24-month CRA. If we hit that 70% three-month CRA with excellent durability as we expect and patients can tolerate the drug out to two years, we have a high degree of confidence we can have a very successful phase three outcome in an adjuvant setting. One final point on the intermediate risk setting is just this. A lot of folks ask us about, what about the reimbursement? Buy-in bill is a strong incentive to use these procedures in this setting. Well, the reality is in the community urology setting where 70 to 80% of patients with intermediate risk antibody-VC are treated, many of these community urologists now have their own in-office dispensed pharmacies where they've contracted with EuroGPO so they can have a spread on oral drugs just like they do for buy-and-bill. That's led to a giant increase in their practice revenue coming from oral drugs, especially drugs like Xtandi. And some patients are seeing upwards of 50% or more of the revenue coming from these oral drugs today. So there's a strong incentive for the physician. There's a strong incentive for the patient. It's really great alignment. And really no one's brought an oral treatment to bladder cancer in this setting before. We've got the oral prostate cancer drugs being used in this setting very successfully. This will be, I think, a game-changing and revolutionary first. So just a couple other points before we get to Q&A. We had our first patient dosed in UTUC that we announced today. This is very exciting. This is actually a study that we anticipate moving to our first approval. That's because the registrational path is a bit more straightforward. Gelmito was able to get to full approval with a 70-patient single-arm study. A little bit about this disease. It's a rare disease, about 3,000 patients. 85% are FGFR3 positive. What we're talking about is the same lesion in the bladder that drives non-muscle invasive bladder cancer at intermediate risk, but the low-grade lesions showing up in these ureters and the renal pelvis, where it's very hard to access with surgical devices. So most tumors are missed, leading to many patients, nearly half, getting a nephrouretorectomy or their kidney removed. Where treatments are used, it's in an effort to save the kidney or to spare the kidney, but you still see high rates of recurrence because of how hard it is to actually access and remove these lesions. The one approved therapy is the chemo and the gel, gel mito. This had a CR rate of about 58%, a duration of response of 56%. So about one in three patients are actually benefiting. You can see here, this isn't without a lot of challenges. This bag and hole that's essentially drilled through the back to try and get the chemo into the renal pelvis is not comfortable or easy to deal with. It's only addressing a small number of tumor sizes. When people ask us, why is this a blockbuster opportunity? A drug like Gelmato is only doing maybe 100, 125 million in sales. There's really a few key drivers. One is gel mito is priced like chemo in a gel. There's certainly premium pricing here that we're seeing in the high-risk setting that's very acceptable to spare an organ. So I think you can look at a four to five X increase in potential sales with a premium and innovative product. Additionally, only about half of patients can really be addressed with gel mito because if your tumor is bigger than 15 millimeters or if you're in the ureter, you're not indicated. So now you're talking about an opportunity that's potentially 10X, what we would see with gel mito. The last thing is really the ability to change the patient experience, not just in the first year, but for years on end. This could become a prevalence population of patients that have truly spared their kidneys and all the comorbidities associated with that that would stay on drug, not for just a year, but potentially multiple years as an oral drug staves off recurrence. so we're in this study SURF 303 we're guiding to initial data next year we're testing two doses one dose overlaps with the IRN MIBC setting one dose that's a little bit more finally in achondroplasia just highlight that we had an exciting announcement today we are cleared on our fourth dose that means we have kids at least three or more that have been dosed at each of the doses the four doses we're testing in our safety sentinel cohort it means that the patients that or the kids that have been going into cohorts one and two are now eligible to be receiving any of these doses when they come up for treatment after their six-month run-in. And we'll be reading out a six-month efficacy dose response analysis from the Safety Sentinel in Q4 of next year. We shared something really quite interesting and exciting. This is an early scientific experiment, but it showcases what FGFR3 selectivity could do. This was data that one of our scientists shared this past week of prenatal dosing in an achondroplasia model. Synchondroses, when these are essentially the growth plates of the foramen magnum, are often fused at birth. We see this preclinically in the animal models. What that means is that that foramen magnum stenosis that can lead to significant surgeries in these kids that contributes to the 50-fold to 100-fold increase in sudden infant death syndrome is really driven by something that happens late in the third trimester. so we actually treated uh pups and their their moms with dabogratinib in the third trimester and where uh wild type expectation for synchondroses fusion is a zero when you look at this this model of pups with acontoplasia the synchondroses fusions are up in the threes or fours with treatment with dabogratinib uh right after birth we see a nice reduction but if you combine that with prenatal testing and afterbirth treatment, you see that on the far right, you can see we've almost entirely normalized reducing or removing fusions of the synchondroses in this animal model. So a really exciting and compelling result that can be achieved with an FGFR3 selective drug. So that's that. It's a great setup for data and opportunities, and Jason, happy to answer questions.

And boy, do we have them. Thanks for the great presentation, Todd. But maybe to start, you've outlined what you're looking for in the readout in NMIBC. Can you help us frame what sort of safety profile is ideal, particularly given sort of this is an elderly population, they tend to be a little bit more frail because they've been smokers? Yeah.

We like to point to a data set of 22 patients that were treated at either 40 or 60 milligrams. These are metastatic patients. from our SURF 301 study. That, there was a rate of low-grade diarrhea at about 18%. We had noted one ALT event that was at 5% that was increased. Really nothing else of significant concern there. Very low grade three events. So that's the type of profile that if we can replicate here now in the intermediate SNMI-VC setting would be just a huge success. Now, investors ask us, well, that seems like, well, what about the diarrhea? Isn't that problematic? You know, one thing we point to is you can look at, there's several studies that Xtandi has done versus placebo. This would be a similar elderly patient population, and obviously it's males, not females. But placebo rates of low-grade diarrhea are upwards of 20% in some studies. So getting to something around 20% is a huge, huge success. And that would be, again, repeating what we've already seen in the MUC setting. So low rates of ALT, AST is important. If you look at Zestorian and Lexo, these are local treatments. The AST, ALT increases were 15% to 16%. So obviously we would want to have very low rates, certainly look no worse than that. And we anticipate from the data we've already generated, we should be able to do that.

Erdifitinib, again, Thor2, looking at that data, is 60%, I believe, dose interruptions. 80% dose reductions. What do you need to come in at compared to those rates?

Yeah, we didn't have any dose reductions or discontinuations at our 40-60 milligram dose. Now, that's not to say that in a large study we wouldn't expect any. In the pretzel study, the TAR210 phase 2 update, the discontinuation rate was about 10%. So we would be looking for low rates of discontinuations or dose reductions.

Maybe one more on patient preference. I see a lot of puts and takes. Certainly, I think an oral option for males would be maybe a lot more preferable just given the physiology. But by the same token, some of our docs are talking about, well, if a patient is older, maybe we just do the turbid because their quality of life or their length of life left just isn't long enough. you know what's the sweet spot for you and and realistically i mean how much of the market share do you think an option like dabo can capture if uh it delivers as it performs as you expect yeah a key point we like to highlight is we intend to run an adjuvant study an adjuvant study means yes you're gonna you're going to stage grade the patient with turbid up front and make an assessment as to the benefit of then adding on a therapy right if you're adding on an

intravesical therapy, intravesical chemo. It's not done a lot today because it's so bothersome. That same analysis may occur for a pretzel or for intravesical viral vectors. If you're adding on an oral option at that point with the benefit of reducing the likelihood of coming back for a turbid, you could see how this option would be very favorable, not just for patients, but even for the physicians and their workflow and their practice as well.

Makes sense. Remind us again about how many patients are diagnosed at least in the adjuvant setting. And again, if the option becomes available, you think some physicians might hold a patient if they're kind of on the edge there at the border?

Yeah, there's 80,000 new patients diagnosed with bladder cancer. So the majority of those are gonna be in the NMIBC setting, low risk, intermediate risk, high risk until you do the turbot, you're not necessarily gonna know precisely what you got. So that's obviously a large amount of new patients every year. But in addition to that, 750,000 patients living with cancer, and many of those are going to fall in those recurrence groups. So when we look at just the annual addressable population, we think it's conservative to say that's 35,000 new patients seeking treatment every year with FGFR3 positive, low-grade, intermediate risk disease.

Let's pivot to UTUC. Maybe taking a step back, you know, you outlined, I think, pretty compelling opportunity, but this was a shift from metastatic UC. Why is this sort of a better sweet spot for dabble relative to, you know, maybe the broader population and MUC?

There's a really interesting phenomenon that occurs when you look at this population, which is a selection bias away from FGFR3 being the driver as you get into more invasive disease. and you know you could almost interpret that so so in the metastatic setting it's 15 to 20 percent are fgfr3 positive but in the low grade intermediate risk setting it's 80 plus so what's going on well you know there aren't you know 30,000 new fgfr3 positive metastatic patients showing up they're showing up with low grade lesions to me that says fgfr3 is a sufficient alteration to start to drive low-grade lesion outgrowths. And then you typically look in the metastatic setting, there's a lot of commutations. So there's other things you're adding on to start to break that low-grade out into maybe something that's high-grade or muscle-invasive and metastatic. That all points to the best place to start with an FGFR3 selective inhibitor is in the patient populations where FGFR3 is the primary driver in that intermediate risk setting. but the only way to play there is to have a very selective drug with exceptional tolerability because otherwise you know these patients want to live their lives they are burdened by the treatment paradigm of urethral violations and repeat office visits you want that oral to be extremely well tolerated so it can just fit into their daily routine then you've really changed the game for that patient.

John Mito 58% CRA I mean ideally what do you think Davo can deliver here?

So we've tested in market research and what we were really surprised by in the UTUC setting where you're at risk of losing your kidney is that any meaningful CRA, whether it's 30%, 50%, 70%, physicians will use the oral option first before anything else. The way they look at it is if I can address this with an oral option, I can avoid all the surgery, removing the kidney, all the other procedures. Why not start there if it's not working for the patient we've got other options. So what will drive, obviously, increased market opportunity would be the more patients getting to CRs and the more that they stay on it for a long period of time, that obviously grows the market. So we'd love to see that be an excellent CR rate, but anything 30% or higher, our market research suggests we'll get massive uptake because of this being such a preferred option to what they're facing today.

It's fair to say that maybe efficacy should be around what we see from the upcoming NMIBC sort of?

We're starting to hear this dialogue from investors and I think it's a wise one that that's a really meaningful de-risking event for UTUC because there isn't reason to suggest it should be too different. There's experience with Thor 2 in the intermediate risk NMIBC setting. That was a 89% CR, that's exceptional. There's experience with infagratinib in the UTUC space by Serena Mateen. Now, it wasn't as clear-cut. They weren't all low-grade lesions. But, you know, three out of five patients in that study were spared in nephrouretorectomy. They saved their kidneys. And the response rates, even though they weren't all CRs, were upwards of 60%, 70%. So, yeah, I think you can expect this is an equally or similarly responsive lesion. So data in the NMIBC setting can be a really important de-risking event for UTC. surf 303 i know a little bit of ways away but but help us frame sort of what benchmarks you're looking for and what kind of output would make you feel comfortable about moving forward in in utuc yeah as i mentioned that the cr rate can be lower here 30 or better um we are testing a higher dose because efficacy could matter more and the willingness to tolerate some uh safety effects is higher given that the alternative maybe you lose your kidney or you know you end up with a hole in your back and a bag to put the chemo gel or, you know, some pretty invasive surgeries.

Got it. Time we have left. Let's go to achondroplasia. You know, if you talk to most prescribers, AHV seems to be much more secondary. I mean, yes, there's quality of life issues, but for them, it's really the medical sequelae associated with that sagittal spine and the Boeing and whatnot. So based on the murine data, how much do you think Dabo could improve upon those metrics? And what does that look like to the competitive field now, understanding we're still waiting for some data?

Yeah. So I think the murine data gives us really exceptional hope that if you tune that FGFR3 activity back towards something that's more typical, that you can really very early on start to normalize many of the growth parameters across craniofacial, foramen magnum stenosis, spinal stenosis, and obviously the long bones, which will drive your AHV surrogate endpoint. Biomirin just shares some really exciting data, and it looks like they're going to go to the FDA to get full approval, which is great. And that data shows that over time, that AHV benefit that seems to be maintained for multiple years starts to lead to meaningful changes in proportionality, tibial bowing. So what's exciting for us is if we can start to hit an AHV difference from placebo, that's more typical of actually changing this to someone without ACON. And that, for us, the target is you want to hit about a 2.7 centimeter per year, not the 1.5 to 1.7. so it's almost a doubling of the AHV, that should directly lead to faster time to hitting these endpoints. Could even give us an opportunity to see in a 12-month randomized period actually hitting endpoints that others haven't. So we're really encouraged by that data. We're obviously looking at what are those endpoints that we might now look at in a 12-month randomized setting if we're really hitting the AHV mark that we want, which is to nearly double it.

Got it. Maybe a little bit premature, but let's throw this out there. do you think that level of growth could drive maybe premium pricing?

Yeah, I think a little premature. Obviously, we've seen what Transcon has done with their pricing. We'll see what BridgeBio does. I mean, look, this is, we're looking to really provide the best-in-class solution. And, you know, there's already, I think, a great market here. Our market research, yes, I suggest you could offer a slight premium by obviously beating these benchmarks. You know, that's something that could go into consideration. But really, the focus is on, you know, for us, it is important with this program that we demonstrate best-in-class activity. We'll be the fourth to market. So that's, you know, necessary to be successful here.

Well, with that in line, last question. Help us frame the output end of the year. What are we looking for to make you confident you're best-in-class?

It really comes down to at the highest dose or the highest two doses, beating the benchmark set by others at six months. Those AHVs were in the low sixes for Biomarin, you know, for Ascendis, in the high sixes for BridgeBio. So we're looking for a dose response curve that clearly points us into the sevens, potentially eights at that six-month period.

Perfect. Todd, thanks so much for joining us. Thanks, Jason. Appreciate it.