From the Cantor Fitzgerald Biotech Equity Research Team, very pleased to introduce from Tourmaline Bio, we have Sandeep Kulkarni, the Chief Executive Officer, so thank you so much for joining. Maybe a quick snapshot of Tourmaline, for those who are less familiar with the company, and some of the milestones we have to look forward to. Sure, Josh, it's my pleasure, and thank you for hosting us. It's great to be on stage with you and to Cantor for having us here at the conference. So Tourmaline Bio, we are an inflammation-focused company based here in New York City on 24th Street. Our mission has been very simple. We're looking for drugs that have standard of care changing potential. Now, our company came together in May of 2022 around an anti-IL-6 antibody that we licensed from Pfizer. There's been a fair degree of commercial and clinical success with IL-6 inhibition over the last decade plus. However, there are a lot of new insights that have only come to light in the last handful of years that we think we're well-positioned to take advantage of. The antibody itself, pacibekitug, has great properties. We think it has a strong claim to being the best in class IL-6 inhibitor. It is long acting, it is fully human. Most of the data we were getting from Pfizer was with every eight-week subcutaneous administration, which we think we can even push out even further to every quarter, which we're testing in one of our phase II studies for cardiovascular disease. So we're really excited about the program. We have a number of big indications to go into with an exciting year of data coming up in 2025. What was Pfizer doing with the program, and what are you doing different, aside from moving from Q8 to Q12? Absolutely. Pfizer, in their hands, were looking at the antibody for lupus and Crohn's disease. There was signal on both of those studies, and particularly the Crohn's trial, which showed a high placebo-adjusted CDI remission rate, which compares very favorably to other novel mechanisms in Crohn's. However, what we understand from folks at Pfizer was that there was a desire to reprioritize or prioritize their oral JAK inhibitor franchise, and so this program was put on the shelf. Now, fast-forward to 2024, as I mentioned before, there are a number of new insights about the IL-6 biology that have only come to light in the last handful of years. Those have only emerged after the point at which Pfizer had deprioritized it. We're really taking advantage of kind of cutting-edge science here to prioritize where we're going with pacibekitug. How did you think about, you know, the I&I landscape and figuring out, you know, what is increasingly a competitive landscape? Yeah Where IL-6 biology best lends itself to give you not just a positive trial, but a differentiated data set? Absolutely. I mean, I think this is, like, an exciting time in autoimmune disease, where, you know, twenty years ago, we may have said, "Well, inflammation matters," but now we're really dissecting out, like, what are the mechanisms in any given, any given disease? So any given mechanism may not work in every indication it's gonna be tested, but this is where, you know, I think there's a number of ways for us to triangulate and get confidence about the indications we choose to pursue. For us, we internally really do value clinical evidence. It may not be a pristine phase II trial, but off-label case reports, genetic validation studies, other clinical trials, like, where we can get confidence that there's real signal here that can be reproduced in a, in a subsequent phase II or phase III study here, and so in the case of the two indications that we're looking to pursue, thyroid eye disease and atherosclerotic cardiovascular disease, these are very different indications, which I think speaks to the fundamental importance of IL-6 as being a driver of inflammation and kind of disease pathophysiology in both of these areas, but this is, you know, girded by just very strong data. In the case of TED, a ton of publications, a lot of patients who've been dosed, who've been reported in the public literature. Our investigators in our trial have used IL-6 pathway inhibitors off-label, have seen good evidence with it, and are eager to be part of the trial to really formally define how it could fit in. In the case of CV, it's just a wealth of information looking at, the epidemiologic data in terms of CRP as a predictor of risk and a very important, marker of IL-6 pathway activation. The genetic validation is, you know, puts us in a very limited, you know, group of mechanisms that has good genetic validation in CV, and then the clinical trial data all kind of points, at this concept that IL-6 may be an important node to be targeting. Can we, why don't we stick on the cardiovascular indication? You recently started the TRANQUILITY trial. Maybe first you can flesh out for us a little bit about that underlying biology- Yeah And the genetic validation. What does give you the confidence in this mechanism? Absolutely. I mean, I think this is the most one of the most exciting stories, like, unfolding within public health, like, right now. I mean, over the last, you know, several decades, we recognize that lipid levels, like, matter. However, we know that even when patients get to target levels of lipids, people still experience heart attacks, stroke, they still die of heart attacks and stroke. We know that. Now, there's been a lot of, like, belief that inflammation is a driver of that residual risk, and that's from any number of lines of evidence. Again, the epidemiologic data, looking at markers of inflammation as being predictors of risk, along with, with the genetic validation for various targets, including IL-6 here. There is increasing recognition and validation for the idea that inflammation, in its own right, independent of lipid levels, LDL, LP little A, is a strong predictor of risk here, and the evidence is emerging to say that IL-6 is an important node to be targeting here. So what is the CHIP variant? How does that validate the target? Right. So CHIP is the clonal hematopoiesis of indeterminate potential. And so this is a new biomarker that's been explored. It's essentially like a genetic signature, you know, that the, that the field believes may confer increased inflammatory inflammation, like risk. CHIP has been seen not just in the context of, like, cardiovascular disease, but even in certain types of myeloproliferative neoplasms, other types of hematologic malignancies. Things like Tet2 mutations fit into that category of CHIP. So there's a lot of interest in looking at this as maybe a way to kind of enrich for patients even further, for who is likely to benefit. In the risk clinical trial data showing that in patients who show evidence of... CHIP, like clonal hematopoiesis, there may be increased sensitivity and benefit that can be seen with a direct-acting anti-inflammatory, like an IL-6 inhibitor. So it's an area of active, like, interest that we're going after. However, we think even a somewhat blunt tool, looking at high-sensitivity CRP, appears to be a very strong predictor of residual risk. Unfortunately, this... It appears that 40%-50% of people who have evidence of cardiovascular disease appear to have elevated levels of CRP. So even a blunt tool, we think, is a strong predictor of risk that begs the question of how can we like manage that modifiable risk? Okay. Does elevated hs-CRP... I guess you've indicated its association with cardiovascular events. Yeah. Is it also separately associated with atherosclerosis in particular, or is it more in patients with established atherosclerosis? It's a vulnerability marker for events? Right. So, let me take that a couple different, like, ways. In terms of like, the kind of non-clinical biology here, there is strong evidence to believe that IL-6 drives plaque formation, plaque progression. That's been, like, very, like, clearly, like, shown. Now, in terms of whether this matters in a primary prevention versus secondary prevention, setting. There's data in both areas. In fact, most recently, there was a publication from Dr. Paul Ridker, that was published in The New England Journal, looking at 30 years' worth of data from 28,000 women who were enrolled in the Women's Health Study. The impetus to do the Women's Health Study was it was a recognition that we tend to under-diagnose or misdiagnose cardiovascular disease in women. So the NIH kicked off this trial in the early 1990s. Now, in the publication that just came out, it does appear that looking at, like, Lp(a), LDL, and CRP, it does appear that CRP may be the strongest predictor of risk in that primary prevention, otherwise, like, healthy group of women, which I think is really quite remarkable. It just speaks to the kind of importance of long-term inflammation as being, you know, bad on the, you know, vessels of the heart and vessels more broadly here. Did we learn anything meaningful at ESC to help inform this program? Yeah. So that was. And this was the big publication that we were really excited to see. What you just cited? Yeah. Yeah. It was published as a late breaker, and then simultaneously- Yeah Published in The New England Journal. But when we go to ESC, we don't have to persuade people that this is, that inflammation matters. In fact, I think there's clear recognition that inflammation is important. It crops up in discussions on HFpEF, acute heart failure, arrhythmias, of course. Yeah ASCVD. Really think this is a sea change in folks recognizing that inflammation is this axis that we just have not well addressed to date. Okay. What, maybe just review the CANTOS trial and what we learned from that, that's helping you inform your own program. Absolutely. I mean, the CANTOS trial, we think, is a watershed moment for this concept that a direct-acting anti-inflammatory can derive residual, like, cardiovascular benefit. Now, in the CANTOS study, which was. The top line came out late 2017. Novartis demonstrated that Canakinumab, an IL-1 beta antibody that sits upstream of IL-6 and is only a partial inhibitor of IL-6 signaling, yielded a 15% risk reduction in terms of MACE. Now, 15% is in line with what we've seen for other novel mechanisms in outcome studies, including, the PCSK9 inhibitors, bempedoic acid, so it's already in the ballpark. Now, in the subsequent analysis from CANTOS, the investigators reported that the risk reduction appeared to be greatest in the patients achieving the greatest reduction in CRP and IL-6 levels, which then begs the question: Why not block IL-6 directly? Now, again, in the field, this was viewed as a real, like, watershed moment to prove that a drug that didn't have impact on LDL, did not have impact on blood pressure levels, but was directly impacting inflammation, was able to yield this kind of this degree of benefit. So now we're at a very interesting stage where you know others have kind of taken like have looked at these data, us included, believe that this is really worth testing further. There are some outcomes trials ongoing from Novo Nordisk with an IL-6 inhibitor, where they're testing that very hypothesis, whether a direct-acting anti-IL-6 program could yield deeper reductions in CRP, where there's strong data to support that, whether that lead to better outcomes benefit. We're awaiting the results from those studies in the near future. Maybe, we can review the TRANQUILITY trial design and what you're looking to learn from that. Right. So, we've kicked off a phase 2 study, the Tranquility trial, in a high-risk population who has Stage 2, 3, or 4 chronic kidney disease and has elevated inflammatory markers, as measured by hs-CRP greater than two. Right now, we met with FDA in November of last year and came out of the meeting, the discussion, with good alignment about on objectives of our study. It is a hundred and twenty patients across four dose arms, where we're looking at quarterly administration as well as monthly administration versus placebo. We will dose patients for a total of a hundred and eighty days, followed by six months of follow-up. Now, our goals from the trial are threefold. One is to confirm we can dose every quarter. Pfizer had tested every eight-week administration in their earlier trials. Our modeling is very clear that we can dose every quarter. We'll look to test that formally in our study. Our second goal is to pick a dose. We'd want to move into outcomes trials on the other side of it. And then three, and most interestingly, is have enough safety data in hand so that we can be phase 3 ready on the back of this trial alone and go into any number of outcomes trials afterwards, in line with the regulatory precedence we've seen from Novo already. So trial is ongoing. We'll have data from that study first half of 2025. How do you think about, you know, following Novo to the market? They're market? They're already well into their cardiovascular- Yeah outcomes trials. So how do you differentiate? How do you think about claiming share when they do have that first-mover advantage? Right. I mean, I would just take a step back and first say that this truly could be a sea change in how we think about managing cardiovascular disease risk, applying to any number of like indications. This is not tens of thousands, but tens of millions of patients in the U.S., and of course, tens of millions more globally, who could potentially, like, benefit, you know, from a, from a class such as ours. So when we think about differentiation, it really comes along like three lines. So first of all, we do have a long half-life to our antibody. We have human data for every eight-week administration. We think we can get to every quarter based on our modeling. You know, we think that's important, especially in a CV population, where we're talking about prevention, not treatment. Adherence can be a challenge in preventative settings, and a drug that can be given three times per year, we think poses very clear advantages over a drug that requires more frequent administration. Two, is in terms of trial design. In terms of the Novo trials, we think they have designed reasonable hypotheses. We think these are good trials to run. However, we've gotten good feedback from our advisors on our SAB already with ideas on how we can develop more nuanced, more formed trials that go after the disease in different ways, even in indications where Novo currently is going. And then three, which I think is exciting, is just how much white space there is here. If we're right, the IL-6 is bad for the vasculature, and blocking IL-6 is good for the vasculature, that should apply to other areas where things like stroke, AAA, peripheral artery disease, where we know the same kind of underlying pathophysiology is at play, where we can be, you know, be first in those places. Got it. Are you gonna wait for Novo to read out their trials before pulling the trigger on your own outcomes trial? Right. So, so great, great question. Right now, we're focused on our Tranquility study. It's a pretty attractive setup for us, where, with a limited investment, we can be in an area that really could transform the treatment of cardiovascular disease. We're well-capitalized for our phase II Tranquility study, getting data first half of twenty twenty-five, and our cash runs to the end through into twenty twenty-seven. Right now, in terms of outcomes trials, we have a lot of options like here, where, where the outcomes trials that we would think about aren't necessarily as large as other outcomes trials here, just given the high risk baseline the patients do have, and it allows for more efficient trial designs, even relative to where Novo has gone. Like, we think there are places to go even more efficiently, going after really high, high-risk groups of patients. That said, you know, we, we know that this is an area of intense interest. If you look at just the excitement around the GLP-1 space, where a lot of the data for the GLP-1s in cardiometabolic disease suggests that GLP-1 agonism may have an anti-inflammatory effect here. All the mechanisms are yet to be parsed out. However, there is indication to believe that it can drive some degree of CRP reduction and have anti-inflammatory effect here, but there's a lot of companies covering this area. We are speaking with a number of, like, partners here. If there is a deal to be done that, you know, allows us to reach more patients and is good for shareholders, of course, we will pursue it. If Novo validates, highly sensitive CRP as an important prognostic marker- Yeah For IL-6 inhibition for atherosclerosis, is there any reason to think you may be able to get through with a biomarker accelerated approval path, or is that too, too wishful thinking? I think it's a little early for that. I mean, thus far, the cardio division has been clear on wanting outcomes trials. There are a couple approved surrogates that can be used for approval, LDL being one, blood pressure being another. One outcomes trial alone is probably not enough to validate CRP as a surrogate for an approval. Here, however, we've found that the cardio renal division, you know, recognizes the importance of, you know, this area, the degree of disease burden that persists even with good treatments to lower LDL, lower other risk factors. And so, we've seen some openness to looking at other types of, you know, endpoints, including imaging, here. It's probably a little bit too early for prime time. However, we think the field is evolving to, you know, think about what are other ways to measure risk, measure benefit that may not involve, you know, large, long outcomes trials. At some point, you know, and we'll talk about the thyroid eye program in just a second- Yeah But between atherosclerosis and thyroid eye, do you kind of invariably hit a decision tree where you have to choose one, or can they both be viable commercially, simultaneously, recognizing very different price points? Yeah, very different price points. Yeah, we're working through like the sort of examples of drugs being priced at different price points, kind of dual track strategies. We're still working through the details on it, and it's very early for us to comment on, like, pricing strategy, like right now. Worst-case scenario is we have to pick one path or the other, but that is a great, great problem to have, where we're talking about very large opportunities on either side we can pursue. Got it. Well, then, why don't we turn to the thyroid eye program, and you know, what is it about the literature and support for IL-6 and this indication? Yeah that gives you the confidence to go into what is a somewhat competitive landscape, but one that will be presumably intensifying in the coming years? Absolutely. I mean, as I mentioned before, our guiding light here is look for clinical data and the terms, and try to position medicines that can be standard of care changing. We think we absolutely can do that with pacibekitug in TED. We if you just take a step back and kind of look at this market, I don't think anyone fully appreciated how much unmet need there was here until there was an approved option on market. However, four-plus years into launch of that drug, what we see is not every patient is getting it. Their unmet need persists here, and we think there's a clear kind of recognition of what that drug is good at doing, what the limitations of that class, like IGF-1R. When we think about an IL-6 inhibitor, we think we can really be standard of care, changing that first treatment option that physicians want to use. TED is an inflammatory autoimmune disease. Patients present hot, swelling, redness, pain, where there's recognition that getting the inflammation under control is of, you know, clear, like, value. So from that point of view, like, we think with an IL-6 inhibitor here, we can offer a drug that, you know, aligns with how physicians think about treating autoimmune disease, whether RA, lupus, Crohn's, any of these indications, physicians think about getting inflammation under control, like, quickly. Now, with a drug like ours, pacibekitug, we think we can, you know, offer an easy-to-use, every eight-week subcutaneous option to get that control of the inflammatory process with a safety profile that's been well characterized from the hundreds of patients of data we have from Pfizer with our drug and other indications, plus all that we know for IL-6 inhibitors in thyroid eye disease. Now, what we found compelling about going here is just how much class experience there is, where it's not just one publication from some random part of the world to say this makes sense, but it is 50 publications, 350 patients worth of data. Many of our investigators who are part of our trial have used IL-6 inhibitors off-label and have seen it do good things for patients and are eager to keep using it and are eager to kind of formally prove out how effective, you know, that is. So as we kind of think through how the TED kind of market evolves, you know, most physicians think about diseases not in terms of what is my silver bullet to cure it, but more, what do I try first? What do I keep in my back pocket? We think we can make a compelling case with a drug like ours, as a long-acting, well-tolerated, subcutaneous, anti-inflammatory to really control disease early and keep that other class in your back pocket for patients who may not respond. Okay, maybe you can review the phase 2, 2b program design, and as we think about interpreting the data, is there a bogey where that you need to be above- Yeah. Thinking about the competitive dynamics? Sure. It's our pleasure. I mean, we, we met with FDA in May of 2023 to talk through our trial design. Now, we've designed it to be a pivotal study, have gotten good alignment that this can count as one of two pivotal trials. So the trial in total is 81 patients, 27 patients per arm, so three arms in total, two active versus placebo. Period A will look at efficacy of the drug, measure the primary endpoint at week 20. Patients who, after the complete Period A, can enroll into an open-label portion where they can receive drug, depending on the response to their Study A assigned treatment, or just be followed off any medication to track for safety. Here, again, this is meant to be one of our two pivotal studies. We know what the regulatory precedent is. It's to use proptosis response for regulatory purposes, so that is the primary endpoint of the study. But what we hear very consistently from TED prescribers is that the disease is heterogeneous. Patients present differently. Proptosis is the bulging of the eye, may not always be present, and even when it is, it may not be the chief complaint that the patient has here. So we think we can, you know, develop a drug where there's good reason to believe that the proptosis benefit will be, you know, compelling, but be able to look at the other things that matter, that we know matter to patients. So diplopia, the inflammatory symptoms, eyelid retraction, all of which are cardinal symptoms of TED that we think we can differentiate on. Again, like, when we think about... when we take a step back and think about what's the medication folks want to use first, it may not be the same drug for every single patient. Really, it's like thinking more holistically about what does my patient have? What is the right drug to use for that, for that specific person? What might features of the patient and disease presentation be that would push them to IL-6? Yeah Pathway as opposed to, like, IGF? 1R? Yeah. Yeah. Yeah, we think first and foremost, it's inflammation. Like, when we look where IL-6 has worked in the literature, it's RA flares, it's cytokine release syndrome, the context of CAR T administration, it's COVID infection, really highly active inflammatory states. So when we think through, like, where do we go into TED? We're going out of our way to enroll patients who have active inflammatory disease, and we're confident that that is the case. So that's a combination of looking at a high clinical activity score, which is a marker of inflammation in TED, capping the number of months since onset patients are to make sure they are still within that active inflammatory window, requiring them to have a positive thyroid-stimulating immunoglobulin test, which just avoids any uncertainty about, does this person have TED or not? So these factors all kind of play into going after people who are in the midst of an active disease flare, where going after IL-6 makes good sense, and that's frankly, I think, where the literature has shown the most benefit for this pathway to date. One of the things Tepezza has shown is that, you know, after an induction course, there is a very prolonged benefit that patients benefit from or experience, I should say. The IL-6 literature, does it show something similar, or do you think it'll be more of a chronic therapy compared to Tepezza? Yeah, let me give you how I think about the IGF-1R class. As I mentioned a couple of times, like, we view TED to be an autoimmune inflammatory disorder. I think that's pretty clearly established. The impact of IGF-1R blockade on that inflammatory cascade is less clear. There's not a clear impact on the autoantibodies that we know play a role within TED. We also see that the durable effect has not been 100%. In fact, in the pivotal trial for teprotumumab, the first approved drug for TED, you see about 40% relapse rate in the year when patients come off drug, among patients who achieved a response initially. So which we think speaks to the fact that the underlying autoimmune disease here continues on, and it makes sense, like, why patients do have a reasonably high rate of relapse. We've seen that in real-world usage as well, where 20%-50% of patients either relapse or require additional treatment here. I mean, this is one area where we're excited to test IL-6 inhibition formally, given that the data for IL-6 inhibition, albeit has been piecemeal. However, overall, the relapse rates have been quite low, sub-10%. Now, I think this gives us the chance to, you know, prove that out or at least shine some more light on what the durable effect looks like by going after the underlying inflammatory disease, but also open the door where in situations where the inflammation persists, longer-term dosing may be, you know, may be needed. Now, we think we can offer that flexibility, given we're an every eight-week simple subQ injection. There's good class data for IL-6 in TED, as well as, like, in other indications to kind of give confidence that this is, you know, can be well tolerated in the right patient. So that's data we'll have to generate here, but we're excited to kind of think through, you know, is there a better paradigm here for patients with TED? I guess hearing loss is one of those significant liabilities- Yes. Not common, but still, it can be an issue for the IL-1 receptor antibodies. From the experience, with IL-6 antibodies in thyroid eye, are you seeing any rate of hearing loss, or has it been- No, I mean, there's no, there's no evidence that we're aware of in the literature implicating IL-6 blockade on hearing impairment. Okay. That compares against the IGF-1 literature, where IGF-1 is an important metabolic growth factor. It's involved in development and function of the inner ear, including the hair cells in the inner ear, which may not regenerate if those cells were to die off, and that may explain, like, why at least some percentage of the hearing loss that's been observed does appear to be irreversible in nature. And so that is a question mark. Now, we think the safety kind of concerns coming up from blocking an important metabolic pathway aren't just hearing loss. It certainly is important. That is real. However, we've heard, seen things like hyperglycemia, including cases of ketoacidosis that have, you know, occurred, menstrual cycle changes, which may be permanent in nature, encephalopathy that's been reported in the literature here. So, there are any number of reasons that we think are, you know, giving physicians pause about, is this the right class to try first? Now, this is where, going back to the point about sequencing, we think we can make an argument to say an IL-6 inhibitor makes sense to use, like, first and keep that other mechanism in your back pocket. And the overall, like, literature for IGF-1R blockade does suggest you can wait 6 months, 12 months, maybe multiple years, and still see that same kind of benefit. So there may not be that need to use to treat right away, and a drug that we think is safe, well tolerable, will get used a lot more, especially among, like, the more community-type docs, where they've not shown, you know, a kind of propensity to use IGF-1R blockade, despite it being the only game in town for four-plus years now. Any thoughts how the FcRn antibody class may fit into the thyroid eye landscape and, and what the implications might be for an IL-6 target approach? Yeah, I think we'll, I think we'll have to see. Like, as you probably, like, know, I was COO for Immunovant for a period of time and helped launch the TED trials, so this has been an area of personal interest to me. When we look through the data that's been generated to date, before their trials were stopped early, what we see is some improvement on apoptosis, but less clear impact on the inflammatory symptom series measured by CAS, where the response - the dose response isn't as clear, the kind of time course to benefit is, kind of fluctuates. So, it kind of speaks to us that this may be, a mechanism that works on certain parts of the disease but may not address all of the parts of the disease. In any autoantibody-driven disorder, there's gonna be varying contributions from other factors, including the autoantibody itself, of course, but the inflammation that presents, the T cell component, the B cell component as well, and the relative importance of those things may vary over time. Now, why we like IL-6 inhibition is that IL-6 is polymorphic in nature. We know it has impact on different cell types, including T cells, B cells, the innate immune response. We see good reductions in autoantibodies from other IL-6 pathway inhibitors here, so we think this could lead to a more comprehensive control of disease beyond just doing a single thing, lowering autoantibodies alone. What, what are the timelines for the phase IIb slash pivotal program right now? Yeah. Right. So we kicked off the phase IIb SPIRITED study, and that is a pivotal trial that kicked off late 2023. We've guided to data from that study in 2025 for that trial. Now, the regulatory precedent for TED is two pivotal studies, and so it's always been our intention that we'll run two pivotal trials. We are capitalized to run a second pivotal trial, which will kick off later this year, which will look very similar in design to what we've done with the first trial, the SPIRITED study. Data from that trial expected in 2026. I guess, like, as we think about that decision tree point- Yeah Where you may have to choose between- Yeah cardiovascular and thyroid eye, how do you think about, you know, starting that second pivotal... Would you be ready to just kind of stop a program because you've strategically made a choice? Do you kind of feel like you'll run both trials out to- Yeah - Filing suitability? Yeah. Like, when do you kind of make that choice? Right. I think it's a great question. It's a tough question. I think it's also a good problem to be in, like what we're talking about- Yeah You know, looking at data from two indications and deciding, like, what makes the most sense. As I mentioned before, like, we do think there is a way to be able to commercialize a priced drug in two different areas. But this will be a data-driven decision for us to say, what's the path that we want to choose if we need to pick one versus the other. How are kind of the analysts who currently cover the company modeling this? Are they kind of choosing one or the other, or are they kind of, are they modeling both? Yeah, I mean, I think, I think actually more like the buy-siders. Like, we get a lot more questions on, like, CV and- Yeah Without naming names, but there are some investors who I think only own us for the CV part of our story here. And so this is an area that, as the data continues to come out, like, hardly a week goes by where there's not a new publication on inflammation, on CRPs being a predictor. It is a, an exciting, exciting time on the CV side. So I, I would say earlier in the year, the questions we get was mainly TED focused with, you know, CV being the last few minutes. Now it's probably more balanced, maybe a little more skewed towards CV, but, it's an area that we think is really exciting, where we can offer two very different indications, different risk profiles. It's incredible to say that this could work in either both of these. All right, excellent. I think we're out of time. So thank you so much for coming to share some of the Tourmaline story. My pleasure. Thank you. Looking forward to these updates.