Good morning. I'm Stacy Ku, one of the Senior Biotech Analysts at TD Cowen. With my colleague, Vishal, we'd like to welcome Jesse Shefferman, CEO and Co-Founder of Protara, as well as a hello to the rest of the team listening in. Jackie, who's the Co-Founder and Chief of R&D, Patrick, CFO, William, CCO, and Justine, Head of IR. Protara has made a lot of progress this year with a catalyst-rich H2 in 2027, and I'm looking forward to digging in. Jesse, we know you have a broad pipeline, but today we want to focus on TARA-002. It's an immune-stimulating bacteria, Streptococcus pyogenes, which we believe is de-risked with clinical data and also with a long history as an ex-U.S. product, OK-432. This is an oncology summit, so we spend the majority of time on 002's opportunity in NMIBC. Just given the recent FDA update in Lymphatic Malformations, maybe very quickly, Jesse, could you talk about the regulatory path for TARA-002 and LM? How are the interactions with the Office of Therapeutic Products? Is there already high awareness, given this is the same review division as NMIBC? Yeah. Thanks, Stacy. Jump right in. Yeah. Thanks, Stacy, and thanks to the Cowen team for having us on. It's been a great partnership over the years. Look, I think we are delighted to have actionable feedback from the FDA on the LMs program. Folks like yourself have for a long time kind of been making the case that the Protara value proposition extends beyond the NMIBC program. Of course, we're as dedicated as ever to that program. Obviously now we're able to articulate a second leg of the stool. Later this year, we'll talk more about choline as a third leg. To answer your question, we were transferred to the Office of Therapeutic Products sort of proactively. We found out about it after the fact, and that was from the Office of Vaccines. Really the way that I'll articulate what does this mean. The first thing I think, again, this is speculation, right? We just sort of can go by our gut instinct. The first piece is OTP is probably, on any given day, reviewing the most cutting-edge therapeutic programs coming through FDA. This is where CAR-Ts are evaluated. It's where gene therapies are evaluated. Sort of just normatively, it's where I think this is a review division that is facile in looking at small populations, looking at smaller end studies, and drawing sort of definitive conclusions from that. Right, when you're in the vaccines division, you're looking at population-based studies. Here, I think it's a division that's more appropriately attuned to the data set that we now understand to be and are confident will be the data set evaluated for STARBORN-1, STARBORN-1 being the basis on which the program's evaluated. I just want to make clear. Beyond that piece, obviously, it's also where the NMIBC program is. There's some frictional components that previously existed where OTP and vaccines needed to be in touch. That's now out of the picture, which I think just makes it for a more streamlined review. As the review team on LMs within OTP has questions, particularly, I think, around safety, and some of the other elements like of a BLA such as CMC or Clin Pharm, there's enhanced ability for crosstalk. I just want to reiterate what it is that we have heard from the FDA and what forms the basis of our ongoing discussion with FDA under our breakthrough therapy designation. They have stated that they will evaluate the risk-benefit profile of 002 in LMs based on the results of STARBORN-1. They have not requested any changes to the sample size or the endpoints of the STARBORN-1 trial. They have not requested an additional pivotal study. Additionally, they've confirmed that our non-clinical package is complete, and that no additional reactogenicity or immunogenicity studies are required. Again, this is a great moment for us in the LMs program because we have actionable feedback. We'll continue to enroll the study. We just put interim durability data out on the STARBORN-1 study at ISSVA about one week ago. It feels like there's a significant amount of momentum there. Of course, underappreciated the manufacturing dynamics where you all had to kind of get the manufacturing in line before you could even start the clinical trials. Yeah. You commented on the interim durability. Sounds like you all have guided to complete enrollment by the H2 of this year. Just very quickly, what does the efficacy of durability look like? What is the result so far? Yeah. 83% of the participants that have completed treatment achieved clinical success. Clinical success is broken into two sort of, let's call it objective measurements. The first is, are these patients achieving a substantial response? Which is defined as 60%-89% reduction in the lesion volume as measured by MRI. In addition to substantial response, there is the component of complete response. Complete response is 90%-100% reduction in lesion volume. 83% of the participants are achieving that clinical success so far. Of the patients that were assessed at the eight-week post-treatment time point, 100% of those patients achieved clinical success. Obviously, we're demonstrating a pretty substantial effect size, frankly, higher than that observed in the University of Iowa data, which a lot of folks look at from an OK-432 perspective. There, those patients across the board achieve about a 63%-64% clinical success. As we look at the efficacy of TARA-002, as we build the STARBORN-1 data set from both an efficacy and safety perspective, we're looking closely at whether there's something about our very exacting manufacturing process that is yielding potentially, a slightly better option for patients. I guess to round out on the durability front, which I think is important, seven participants so far have reached the kind of 32-week post-treatment assessment time point, and all of those patients remain disease-free. Again, I think what we're looking at here is a durability that is in line with the initial kind of significant response and effect size that patients are achieving. Okay. Wonderful. From what we recall, you said, OK-432, some of the results from the Iowa study have gone out to six to nine years with good durability results. Yeah. That's right. Just for some background, as we think about the results in totality, where do you think TARA-002, just had a KOL call, which was really insightful, is going to be positioned among the macrocystic mixed LM patients versus the current options of sclerotherapy and surgery? Yeah. Look, I think we get this question a lot, and I want to make sure that we're properly contextualizing where TARA-002 fits relative to what the current treating community deems as a useful treatment. Specifically, we're talking about, for lack of a better term, sort of chemical ablative agents that are indiscriminate in tissue destruction and remodeling. Often referred to as sclerosing. Some docs refer to it as chemoablative. Be that as it may, what we know is that those regimens are effective at managing lesions, but they do not provide a level of complete resolution that we're seeing with TARA-002. Remember, these are chemicals that are indiscriminately used to sort of destroy tissue. What we know is that there's a pretty significant recurrence rate. There's no real one modality or standard modality by which they are given. I also want to point out that one of the things that we are learning, and this has been my experience in rare disease across the board. As you kind of get deeper into your pivotal study, you get an ever more granular understanding of the patient journey. One of the things that we've observed and actually presented in three different cases at ISSVA last week is TARA-002 is demonstrating a profound effect. Again, like 83% in all patients, 100% in evaluable patients. It's doing so in the case of these three cases in patients that have undergone significant prior treatment and failure, including all of the known chemoablative agents that are used in this setting. That's really important. We showed a case of a three-year-old boy, who had cystic fibrosis as a comorbidity. That's a patient that was actually given compassionate use drug, so won't contribute really to the overall data package for STARBORN-1. That child achieved a complete response of their lymphatic malformation after one dose. Right? That's a kid that failed doxy, bleo, ethanol, Sotradecol. One of the things that we're keeping an eye on is TARA-002's differentiated mechanism. Remember, we're leveraging sort of the very elegant immune-activating components that we know have demonstrated efficacy in NMIBC, here in this same setting. The mutated cells are not necessarily oncologic in nature, but we're still going after a more precise, targeted ablation of mutated cells. I think that as we move into kind of the comparing and contrasting, we believe that we've got a safety and tolerability edge over kind of what's currently being used. We also have a dosing profile that is better. As we think about where to from here, I just was speaking with a really fantastic physician at ISSVA, Jay Shah from Children's Healthcare of Atlanta, and he treats about 160 cases a year. When he uses doxycycline, he has to tell parents that are showing up thinking that those kids are there for an outpatient procedure, that that kid, because of the pain associated with doxycycline and because of the general anesthesia that he has to use for those kids that are smaller that are undergoing that pain, that's a two-day inpatient sort of burden on the healthcare system. Again, as we interface more with the setting, we're coming to understand that, sure, given the armamentarium that's available to docs today, some of these kind of off-label chemoablative agents work, but they're not as good as TARA-002. Look, it's a little cheeky, but there was a moment in time where if you had really high cholesterol, you took Mevacor, and your cardiologist said, "That works really well." LIPITOR came along. Right? What we need to remind folks is that there is always a market for a better mousetrap, and we feel increasingly that based on what we've seen in our own experience, and of course looking back at the OK-432 data, we have a better mousetrap in this setting. Okay, understood. As we think about maybe the size of the LM market, team has done a lot of good detailed insurance claims analysis. What have you all learned there? As it relates to pricing, how should we be maybe trying and building around the opportunity? Yeah. Look, given the efficacy that we are seeing with these kids in one to two doses, in most cases, we've historically focused and sort of guided the street to focus on the incident population, which is about 1,500 live births per year, of which we know the vast majority are going to be macro-associated. Look, the prevalent population here was harder to get our arms around. However, again, as I said, you learn a lot as you go along, and we're looking now at claims data, and claims data that we have observed suggest that there's about 20,000 cases of patients that were previously diagnosed, so obviously falling into the kind of the prevalence bucket, that are seeking treatment. Other sponsors kind of broadly in the lymphatic malformation setting, kind of are citing a prevalent number of about 80,000, and that's probably right, but for our purposes, we think that there's a 20,000 patient prevalent population that are actively seeking treatment. I think, again, I'll refer you to the cases that we presented, whether it was the 1.7-liter cyst patient, the eight-year-old boy who was waiting to fly to Japan to get OK-432 before he came in to STARBORN-1, or whether it was a cystic fibrosis patient, or the other case that was presented, which was a seven-year-old girl that was misdiagnosed as having an LM at baseline, but was really a ranula. The CF patient and the seven-year-old girl both had undergone significant pretreatment, and were in a state of sort of watching and waiting because, once you get to ethanol within that milieu of sclerosing agents, you're kind of at the end of the road, and each of those patients had reached that point. In both cases, TARA-002 was utilized effectively in the case of the three-year-old boy, with one dose, and in the case of a seven-year-old ranula patient about four doses. As we think about the prevalent population, we start to think about the first sort of, if you will, kind of the low-hanging fruit for us are these kids that are in that prevalent population seeking treatment, but not necessarily seeking intervention. We'll know more about that as we continue to dig in, but that's a pretty big piece of the pie that we now feel more confident we have access to, especially as we demonstrate that TARA-002 is efficacious following significant prior pretreatment. There you go, I think, 1,500 is the incident number, that's a new diagnosis, and then 20,000 kind of seeking treatment. As we've often discussed, there is a degree of urgency that gets pretty heightened as these kids reach the ages of two, between two and five, getting ready to go to school, that makes sense. We also are increasingly confident that there is a significant population of people out there, most of them young, not necessarily pediatric, that are very much waiting for something else to come along, and we're excited to be that something else. Let me tackle your pricing question. As it relates to pricing, we know that there are PI3K inhibitors in the microcystic setting that don't provide the same clinical effect size that we've seen TARA-002 demonstrate in the macro setting, and those are priced as high as $400,000 a year. I want to be really clear here. If we are providing what we believe to be significant enhanced effect size and value to patients relative to some of these PI3K inhibitors that are priced at $400,000, we would anticipate pricing 002 based on our relative value and enhanced value to patients and their families versus those other therapies. Okay. Understood. Given the time, let's transition then to NMIBC where, again, I think there is a lot of familiarity with the recent results, the landscape. You all are both pursuing BCG-unresponsive and BCG-naive patients, for both first line and second line, et cetera, positioning the product. Just help us understand what efficacy profile are you seeing as we think about both populations? What's the level of awareness that you all have so far with the clinician base? Yeah. The competitive landscape. Yeah. I think, we believe our efficacy data is competitive with other therapies. You're seeing, whether it's a six-month CR in the high 60s or a CR at any time in the 70s in both our naive and exposed or rather unresponsive population. We feel that we are highly competitive in those approvable endpoints if you will. As durability reads out and the N gets higher, we're very, very confident that we will be in a competitive sort of stance from a durability perspective. Look, at the end of the day, if 002 is going to be sort of competitive or, and among the very highest out there from an efficacy perspective. The ease of use story becomes very important as this entire setting moves from heterogeneously conducted clinical studies to just adoptable products. I would say that in addition to, we often get the question, where does it stack up? Increasingly, we know that 002's broad immunopotentiation is viewed as a third modality in the broad sort of armamentarium of these novel NMIBC therapies. You have either enhanced chemo, targeted immunotherapy, but we now view 002 as being a third option for docs, and we know that cycling is going to be, and sequencing is going to be a big part of the story going forward. We offer something different than maybe what had previously been tried. I think we make a good case for being potentially the first thing that docs provide. Our objective based on our efficacy and based on our product profile, we believe that we are actually the potential backbone of the NMIBC landscape. I guess with that, how do you think the TARA-002 data, especially as it relates to the BCG-unresponsive patient population, do you see that converging with the BCG-naive patient population data we've seen so far over time? When do you think we'll get the next update? Related to the data. What do you make of the competitive enGene data updates that we're seeing as we think about long-term durability? Yeah. Just real quick, I think, you can look at the swimmers plot that we recently put out there at GU ASCO in February, and you should not anticipate us putting out an immature 12-month durability number until the majority of those patients that are evaluable or will be evaluable have read out. None of our competitors published 12-month data until they were fully enrolled, because until you're fully enrolled, all your early failures work against you, right? We don't have a gun to our head. You should think about moving 12 months out from our earliest dated dose patients from that swimmers plot. As it relates to enGene, listen, this is a really, really tough business and any sort of product failure stings, right? It reminds us that we play a risky game here in drug development, but the reward is worth it when you're touching lives of patients. I would just say that this ease of use, tolerability, low impact on the community practice story was one that we once shared with enGene, and now we feel we have it to ourselves. Okay. Understood. Giving us some guidance around enrollment to be completed for ADVANCED-2 in H2 this year, I believe you said comfortably. Yeah. Just help us understand what are the next steps from a regulatory perspective. Just remind us what the regulatory endpoint is, at least for the BCG-unresponsive patients first. Yeah. It's the exact same study that everybody else that has an approved product in the BCG-unresponsive setting was approved on. The single arm open label study with a primary approval endpoint of CR at any time with a key secondary of DOR. It's important. 12-month CR is not a part of anyone's regulatory approval package. That's an artifact of folks trying to cross-compare durability across heterogeneous studies. DOR would be our key secondary there. I think it's premature to talk about regulatory pathway, but obviously, if you are completing your enrollment in 2026, there's a pretty well-rehearsed cadence of the timelines it takes to get to an approval following completion of your enrollment of a study. Okay. Understood. Then you've also been progressing the opportunity for 002 in more of a first-line setting with a H2 slated to start for the pivotal trial. Just help us understand ongoing decisions for BCG-naive versus BCG exposed. We saw you slide that in there. Yeah. Just help us understand how you all are thinking about chemotherapy as a comparator arm, just because there is somewhat limited evidence. Yeah. I think I'll answer those very quickly. The first is, we are good to go on sort of the preliminary population that the FDA agreed to, which is sort of naive, can't get, doesn't tolerate, refuses, and that in its own right is a very large population. For that, we've agreed on the sample size of 284 patients, and we've also agreed on the chemo comparator endpoint. To that end, what we showed FDA was a claims-based analysis that showed what our view was of the efficacy of mitomycin, both in the mono setting, and sort of potentially other agents. We feel that right now, we would not have proposed that endpoint and that comparator, or rather that comparator set and sort of the powering based thereon if we didn't feel that we were very well-informed by the claims analysis that we showed FDA that gave us the green light in the first place. Okay. Understood. Sounds like folks, again, the [inaudible] launch seems to be going very well. They've pointed to, I think, big picture, around 600,000 new patients diagnosed in it every year and another 400,000 that are recurrent. Just help us understand, again, as we think about the potential opportunity in the prevalent population patient cycling to drug versus maybe some of this incidence market that folks are trying to parse through. What do you think is the big opportunity for TARA-002? Yeah. Listen, you can either go way down a rabbit hole here, or you can keep it top of the waves. Let's start with what we know we know we know, which is irrespective of whether a urologist is practicing in a community or in an academic setting, we know that the first order consideration for patients and for these docs is bladder preservation. That will drive a ton of sequencing of these novel agents, and as the only broad-spectrum immunopotentiator in the unresponsive setting and beyond, that leaves us very well-positioned. Right. It's a different mechanism for when those patients recur, and so far, based on other sponsor's data sets, no one has made it to the 12-month time point with more than 50% of their patients still in response. That means, at each given time point, you have an opportunity to step in as a different modality, and that's independent of prior BCG exposure. Right? The big opportunity for us, I think, lies in, look, who knows if it's 600,000 globally for it. These are all really big numbers. Even if they're wrong by an order of 10, right, it's still a large addressable population. There, I think the combination of the efficacy we've demonstrated to date, which is at the top of the range, our confidence that durability will be there as it goes up. The fact that we now are alone in this ease of use and tolerability story that honestly carried a lot of water for one of our competitors. We now own that. I think on top of that, just being able to make it a little bit easier on the practice to be reimbursed, make it a little bit easier on the practice to not have to think hard about what they use. Finally, we believe this setting will look like almost any other indolent chronic setting or other oncology setting, which is where as patients are refractory and looking to preserve a major organ system, right, you will try whatever monotherapy is out there, and then you'll try combo. Just want to remind everybody that TARA-002 has no overlapping toxicities with any of the other agents that are out there. If you want to combine us with [inaudible], you want to combine us with cretostimogene, you want to use us instead of BCG with Anktiva, we have the capacity to be that second agent across the board. I think that is something that is unique to 002. As this setting matures, will be another differentiating factor. Yep. We anchor our thesis around the amount of patients that get a cystectomy and the size of the market there. We totally agree. Well, I know we're going to get also, in addition, an update from the IV Choline Chloride program in the H2. Big catalyst-rich H2 2027 to reiterate. With that, we're going to conclude our discussion here on Protara Therapeutics. Thanks so much for Jesse Shefferman and everyone listening and for joining today. Take care. Thanks, Stacy. Really appreciate it.