Going to read this disclosure statement. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales rep. Elyse, welcome. It's a pleasure to have you today. I think we're going to spend a lot of time talking about your lead molecules TX-forty five. Why don't we start with that big picture? What is it? All right. So TX TX45 is a long acting relaxin mimetic. And when I was in medical school, we used to hear about relaxin as one of the hormones of pregnancy because it's upregulated in pregnancy and enables the pregnant mom to increase cardiac output to accommodate the demands from the fetus. It also has antifibrotic effects that are evident in the pregnant female, because that's what remodels the pelvic ligaments to enable a vaginal birth as well. And so why we think that that helps us understand what it could do in patients where we think it could increase cardiac output in patients with heart failure. It has three major mechanisms because it's really multimodal action. Number one, it's a vasodilator of both the peripheral circulation, but for what we're going into maybe even as important, the pulmonary circulation. It dilates the pulmonary vessels. It's also a leisotropic agent. That was a new term I learned a few months ago. What does that mean? It means it actively relaxes the heart muscle during diastole. And during diastole is when the heart fills with blood. And in a certain form of heart failure called preserved ejection fraction heart failure, the defect is that you have a thick, stiff ventricle that doesn't relax during diastole. And so it can't fill with enough blood, and then there's not enough blood to pump out. And so if you can dilate the myocardium, you can actually improve heart function. And lastly, it's an antifibrotic and a remodeler. It does that by increasing metalloproteinases as well as inhibiting the TGF beta pathway. And so we think it can work in forms of pulmonary hypertension, for instance. And we've chosen a very remember, because I said it dilates the pulmonary circulation. And so we chose, as our first indication, patients who have left sided heart failure due to preserved ejection fraction heart failure, and along with that, have pulmonary hypertension and elevated pressures in the pulmonary arteries. And we're focused within that in another subset. And these are patients who have evidence of high pulmonary vascular resistance. They have you'll hear me refer to that as CPCPH, combined pre- and post capillary pulmonary hypertension. The post capillary part is that you have elevated pressures on the left side of the heart from heart failure, and that flows back into the pulmonary circulation. Patients who just have that post capillary part have IPCPH, isolated postcapillary pulmonary hypertension. But there's a subset that has that CPCBH combined pre- and postcapillary. The precapillary hypertension is almost as if on top of their heart failure, they also have early PAH. They have a narrowing of the lumen of the pulmonary vessels, which restricts blood flow into the left ventricle and a high pulmonary vascular resistance as you try to push blood through a narrower pipe. And so these patients have really reduced exercise tolerance, both because of their heart failure, but also because their high PVR, when they exercise, prevents blood from going into the left ventricle. And that's sort of our first patient population that we're focused on. Right. And it's not a small population. You might just want to give the audience an idea of the size. They're very large numbers. Patients with HEPPAS preserved ejection fraction heart failure in The U. S. Are probably three point five to four million. Of those, patients who have Class II and III, which is severity of disease, and elevated pulmonary pressures, and therefore, pulmonary hypertension is about one point four million. And of those, probably close to it could be up to seventy five percent of those have elevated PVR. So we could be talking about seven hundred thousand, close close to one million patients in The US that have CPCTH. Fantastic. So there's been a lot of news out there in the last week, not specifically about your program, but I thought it might make sense to dive in on the competitive landscape because I think you'll hear some very key differentiators in terms of what Tectonic is doing. But Lilly presented recently at a conference over the last week, and I think it'd be helpful just to give the background in terms of what they disclosed, what are the ramifications for our program, if any, and we'll go from there. And that is the first question that we've been asked all day with investors. So Lilly had a long acting relaxant. It was designed differently than ours. It was a relaxin moiety attached to an antibody to albumin. That's what they used to enhance the half life. It was shorter acting. It had to be given weekly. And they went into a very different patient population. They went into patients with preserved ejection fraction heart failure. That part is similar. Decompensated preserved ejection fraction heart failure. And probably a minority of patients in their study had BPCPH. But most importantly, these patients were decompensated. They had to have been discharged from the hospital within the last two weeks for exacerbation of their heart failure. And what is exacerbation of heart failure that leads to hospitalization? You get fluid overloaded with like liters of fluid. And very often, you're sent out of the hospital feeling better but still fluid overloaded. And what they had a what they found basically in the study, they stopped announced that last January. They just finally presented the data. As they saw, there was evidence of fluid retention in patients who were retreated with relaxant. And there was a numeric but not statistically significant increase in heart failure hospitalizations. Now, we know that vasodilators can lead to some degree of fluid retention. Why does that happen? You get vasodilation, including in the kidney, and the glomerulus in the kidney perceives low pressure, thinks the patient is dehydrated and wants to hold on to sodium and hold on to fluid. So we know that happens. And in fact, there are approved drugs for heart failure that are effective but can lead to some fluid retention. Hydralazine with plus nitrates, a drug called Vidal, which is approved for the treatment of reduced ejection fraction heart failure, is associated with some degree of fluid retention. So it wasn't terribly surprising that you got a little bit of fluid retention. It wasn't much. It was around 200 ccs. But in this patient population that they studied, number one, they can't accommodate any more fluid because they came in fluid overloaded. And the other thing is because of their decompensated state, along with the fact they were just treated with a lot of diuretics in the hospital that's how you treat heart failure they may be more prone to sodium retention. And maybe, theory, maybe could have retained even a little bit more fluid. Hard to know or not. That's a very different patient population to a compensated, stable heart failure population, which is what we are studying. Our patients have to be on stable meds. They have to be euvolemic, meaning they don't have any evidence of excess fluid. We don't want them dehydrated. We don't want them fluid overloaded. That's been something that we've been emphasizing throughout, with the hope that if there is a little bit of fluid retention, they can accommodate that. And all of the other things that the drug does to improve cardiac output, dilate the pulmonary vessels, will be greater than anything that comes from a little bit of fluid retention. Now, there was good stuff that came out of that study. And what was that? And we may have a chance to talk about that. We presented data looking directly at right heart cath and hemodynamics in the heart, and it had very favorable data. This was after a single dose where we looked at hemodynamics for eight hours. And the one question we were asked when we presented that data is, how do you know you don't get tachyphylaxis? How do you know the vasodilatory effects and the leisotropic effects are maintained? And I think that we can put to bed based on the six month data from this study, where there was evidence that the vasodilation did persist. They looked at something I think they called total peripheral resistance. It's similar to systemic vascular resistance. It went down. It remained down. EGFR remained up. They didn't look at pulmonary arterial pressure. They didn't look at pulmonary vascular resistance, two things that will be important to be reduced in our patient population. But I think I'm hopeful that there's no reason to believe those effects wouldn't be maintained as well. Great. Thanks for that. I understand AstraZeneca also has a program in the relaxing actually, two. And they just completed a Phase II. Perhaps you can comment. Yes. So their Phase II with their biologic is being done in a patient population more similar to ours. It's patients with group II pulmonary hypertension, meaning they have heart failure and have high pulmonary artery pressure. They're including both HFpEF, like we are, as well as HFpEF, that's Reduced Ejection Fraction Heart Failure. And they are including patients with high PVR, CPCTH, as well as low PVR in their patient population. Their primary outcome is PVR, pulmonary vascular resistance, looking for reduction in the overall patient population. They also have a small molecule that they're studying in chronic heart failure, stable chronic heart failure. That patient popped and that has three seventy five patients. That's with their oral. Their study in group two pulmonary hypertension just completed. Should have been done in August. The other study in chronic heart failure completed recruitment. Between them, you've got over 600 patients that are on relaxin. And those studies have continued, including we know there is an interim analysis done in the study in group II pulmonary hypertension, where they had right heart cath data. Looking directly at hemodynamics, They could look at something called pulmonary capillary wedge pressure, which is what goes up when you get fluid overloaded. And it's hard for me to believe they would have continued the study had they seen anything that looked like what Lilly saw in their study? That provides me it helps me sleep at night. It doesn't mean that I can assure a positive study, but it's quite reassuring. Great. And I guess lastly, Merck has a product approved in PAH arena for sotatercept, but they also are looking at the pulmonary hypertension arena. Specifically, the CPCTH population. And they should have data probably later this year. I think their study ends in October. We've heard anecdotal reports from physicians who have tried it off label in those patients and have reported their patients have felt better. So we look forward to seeing that data. I have to tell you, we've had people say, Well, I mean, if it's sotatercept is positive, then what is it that's bad for you. I actually don't agree with that. I actually think it's quite positive for several reasons. First, great for patients. It is a large patient population in a complex disease. If PAH, which only has, I don't know, 50,000 to 75,000 patients, can accommodate four or five mechanisms of action, I don't know, almost 12 drugs, CT, CTH. It's always good to have multiple mechanisms. We're in a broader patient population than they are. They're looking at ejection fraction greater than fifty percent. We're looking at greater than forty percent. That forty percent to fifty percent adds about onethree more to patients. And I think there'll be some hesitancy to use tetadercept in patients who are in anticoagulation because of a bleeding risk. And fifty percent of patients with CP, CTH have atrial fibrillation and should be on anticoagulants. So I think there is and then lastly, they've said they're not reducing their price. I can tell you their price point is much higher than anybody thought would be a price point. It just means that it makes the market even larger than I find people. And it's a large market. Great. Good. Well, thanks very much for that. But I think now we'll probably want to dive into the clinical trials. And you've got a lot of metrics that you're evaluating. I'm not sure everyone's familiar with all of No. So I think I remember when you mentioned these metrics and your targeted profile, which you knocked out of the park, but why don't we go through those specifics? Yes. Okay. I know so many acronyms. So what you want to look at our hypothesis is to work in CPCPH. You have to both improve left heart function, and you have to bring the pulmonary vascular resistance down. And let me tell you, in heart failure, why do you have exercise intolerance? Well, when you exercise, you have to increase your cardiac output to get more blood and oxygen to your muscles. But patients with heart failure can't increase their cardiac output sufficiently. And as more blood comes into the heart, their pressures go up. And something called the pulmonary capillary wedge pressure, it's pressures on the left side of the heart that can then extravagate into the lungs, and they feel short of breath. In PAH, what makes you have a reduced exercise tolerance is that because of the narrowing of those pulmonary vessels, when you exercise, you can't get enough blood into the left side of your heart. So it's all about your elevated pulmonary vascular resistance. In CP, CPH, it's both. And so we wanted to see that we were bringing the pulmonary vascular resistance down, dilating those pulmonary vessels. And we wanted to see a 15% to 20% reduction in the PVR. That, in PAH, leads to an increase in six minute walk. And we wanted to see a reduction in the pulmonary capillary wedge pressure, which is a really good measure of heart function, left heart function, and pressures on the left side of the heart. We wanted to see a 15% to 20% reduction in pulmonary capillary wedge pressure. Cardiac output, we weren't sure if we'd see an increase at rest or not. What we saw in our Phase Ib, where we gave a single dose, we did baseline right heart cath where we measure pressures and cardiac output, gave them a dose of drug, then measured it over eight hours, was we saw a or a 32% to 35 reduction in pulmonary vascular resistance in patients that had a high pulmonary vascular resistance. And we saw like an eighteen percent or 19% reduction in pulmonary capillary wedge pressure. Pulmonary artery pressure went down. I think it was 16% or 17%. And upside, another upside was cardiac output went up by about 18%, which we weren't sure was going to happen but really bodes well, we thought, for improvement in six minute walk. Right. Now that trial was not enriched, right, with We ended up with about half the patient had PTCPH and about half had IPCPH. The cardiac output and the pulmonary capillary wedge pressure went down in the whole population. The PVR reduction was in the high PVR patients, which is what our hypothesis was. Because once you're low, you've got a floor We effect if you're also did do echocardiography at day thirty and found evidence I didn't think we'd see much of improvement in right ventricular function as well as a surrogate for PVR also remained it showed evidence of improvement out to day thirty. Okay, great. Now this was Part A of your 1b. Is that right? Part B? That's right. Looking at a slightly different patient population. Now we're going remember, I kept saying we're focused on preserved ejection fraction heart heart failure, HFpEF. Those are the ones with the fixed, stiff ventricle. Part B is in HFREF, reduced ejection fraction That's heart ejection fraction less than 40%. And we're doing a very similar study as we did in Part A. And we'll have data from that October. Okay. Great. And we think it will be helpful to put the AZ data into context since they have both HFrEF and HFpEF in their population. Great. Now you've already started your Phase II APeX trial. Maybe you want to give a description We're as to what over thirty percent enrolled in that study, and we are enriching that study for patients with a PVR greater than three wood units. The diagnosis of CPCPH is PVR greater than two wood units. But we really wanted to enrich for the higher PVR patient population because we think it's likely that's where you'll really see the benefit in six minute walk test. So seventy percent of the patients in our Phase II have a PVR greater than three, and it's likely we'll end up with eighty percent to ninety percent with a PVR greater than two and a very small fraction that have a normal PVR in that study. And the primary endpoint is in that PVR greater than three. And we're looking primary endpoint is PVR, pulmonary vascular resistance. We'll look at pulmonary capillary wedge pressure. We'll look at cardiac output. Patients have a right heart cath at baseline and, again, six months later. And we'll look at six minute walk as well. We're not fully powered for that, like most Phase II studies in pulmonary hypertension, but we'll be looking for a strong numeric trend in that study. And ultimately, for the pivotal trial, primary endpoint is six minute walk test. And I think you did mention very quickly what's been seen before in terms of some of these markers relating to six minute walk. You might want Yeah. There's not in PAH, when you get a 20% reduction in PVR, you get about a 30 meter increase in six minute walk. So we were seeing thirty five percent. That's quite in half past. There's actually not a lot of late heart cath studies. And there's one within SGLT2 where they saw a 20% decrease in the pulmonary capillary wedge pressure. And that, in another study, led to about a 20 meter increase in six minute walk. In our patient population, if you can get ultimately about a 20 meter increase in six minute walk, that's what the KOLs feel is clinically important, we'll be looking for a strong numeric trend in the study. Great. And you also recently announced another indication for PHILD. Yeah. There are five groups in pulmonary hypertension. And PHILD is the pulmonary hypertension that's associated with pulmonary disease. And PHILD is PH pulmonary hypertension associated with interstitial lung disease. That includes interstitial pulmonary fibrosis, drug related lung disease. It doesn't include COPD. So it's patients that have interstitial lung disease and associated with that get pulmonary hypertension. And again, in those patients, if you can bring the pulmonary vascular resistance down, you can get improvements in six minute walk test. And given our Phase Ib data that was so positive on PVR, we thought it really made sense to choose another pulmonary hypertension patient population. It's sort of an orthogonal shot on goal. And it takes and we think that population also takes advantage of the antifibrotic effects of relaxin as well as the effects of remodeling of the pulmonary vessels that we've demonstrated preclinically. And when would you contemplate starting that trial? We'll start in 2026. We haven't given more specific guidance until we finalize the protocol and get a CRO on board. So in the coming months, we'll get those in. We'll give more specific guidance. Great. And what does the competitive landscape look like there? Well, right now, there are the only drugs approved are caprosternals, okay? So there's a drug from United Therapeutics, and there's Utopia, which just got approved. And those are prostaglandins. And then there was that was big data over the last few days for United Therapeutics, where everybody just thought the prostaglandins were vasodilators. That's it. But in their study in PH ILD, they showed improvement in FVC, which is a marker of lung function. And people said, Well, maybe it's having an effect on the lung disease. And so they did a study in IPF and saw great results. It's very exciting for Yes, exciting. Harkening back to Lilly, any ramifications of that trial? We're just starting to talk about it, which is our plan was to do monotherapy only. We talked about the fact that we might want to study it on top of topostanol. So we're sort of relooking at the design to figure out when is the right time to bring in looking on top of topostanol. Because I think if we went into a Phase III study, we'd really want patients who were and were not on capostanol in that study to go after the widest possible patient population. Okay. Any other indications you might be planning? Well, everybody asks us about PAH. Not right yet, but that's theoretically another place we could go. Great. Okay. Any questions on the Relaxin program before we go to your second program, which doesn't get as much airtime as it deserves. Although we're starting to. We're starting to get there. All right. Let's talk about HHD. Okay. So second program, HHD Hereditary Hemorrhagic Telangiectasia. I'm glad you Right. Did Second, it was known as when I was in medical school, which dates me probably by decades. It's the second most common genetic bleeding disorder. Mutations in it's autosomal dominant. Mutations in BMP-nine and BMP-ten. And basically, it's a disease of angiogenesis. Inhibiting by having mutations in that pathway, you get an increase in angiogenesis, blood vessel formation, and they're not normal vessels. And so patients bleed. Most common site of bleeding is nasal nosebleeds. And I can tell you, the first time we went to the board and said, we want to develop a blood they're like, you want to develop a drug for nosebleeds? But these are not like the nosebleeds kids have in grade school. These are nosebleeds that can send patients to an ER and are very difficult to control. And it gets worse as you get older, and you can get GI bleeding. Now they think that women can have very severe menstrual bleeding, which can make them anemic. You can have atrial venous malformations. You can bleed into your head, into your lungs. So it can be quite devastating disease. There's about seventy thousand to seventy five thousand patients in The US, And we're going to go after the fifteen percent to twenty percent that are moderate to severe patients. And there's no approved therapy. You like to choose indications that are high end to unmet need in Mayo approved therapy. Right. So you're, I think, targeting first quarter twenty twenty six in terms of Yes. We're just finishing up waiting on histopath on our tox studies. And we've got drug made. We've got a formulation and start that study in first quarter of next year. Going into normal healthy volunteers, mainly for PK and safety, it's a novel target. And we haven't announced the target yet. Probably around the time the patent comes out early next year is when we'll start talking about the target. But it is novel. So looking at safety will be important PK. And then our Phase II study will be in patients, probably a three month study. And the great thing about HHT, my CMO, Marcy, who you know is a pulmonologist, says it's sort of like cystic fibrosis was, where patients are congregated at centers of excellence in The United States and in Europe, which should make us the fact that we only hope we have to go to a few centers, several centers to find the patients. And we understand they are very motivated patient population because there are no approved therapies. Right. And I believe this product came out of your platform. This product. Let's spend a little bit of time on your platform. Okay. So GPCR is G protein coupled receptors. They're receptors that sit on the cell membrane and act as a way of having signals from the outside get communicated to the inside. Many hormones work through GPCRs. Onethree of all drugs on the market are against GPCRs, but that represents only about 12% of known GPCRs. So there's a lot of biology out there. And almost all of the drugs, except for about two or three, are oral, because historically, making biologics antibodies against them have been very, very difficult. And our platform really enables us to make antibodies against GPCRs. That's really what the company was founded on. Relaxin came from one of our founders' labs and came full of it. And it eased a part of our platform, the protein engineering. We did some creative protein engineerings that our competitors didn't do that we don't have to get into today. But this first was the this target is the first one to fully come from That's our exciting. And I assume we're going to see some other development candidates. We I actually we've got some really exciting things that are further behind it. We're going to not talk about them until we're ready to. But there's some the team's done a great job. And I think once we're ready to start talking, then I think you'll see nothing that we're working on is new to. Right? We're really taking novel approaches, as far as we know, to every disease that we're going into. And we're in a lot of different therapeutic areas because we're not TA focused. We're going after targets where we really believe we can make a difference. Right? So maybe it might make sense, Elyse, with the few minutes we have, just to summarize, I think, a robust news flow calendar for the next year or so for the company. Yes. So I think October, we'll have data from that reduced ejection fraction Phase Ib study. That's a single dose study, but we'll have data out to a month. We think the important thing in November will be to see if it's on their pipeline or not. And hopefully, there'll be data from that. I mean, maybe as early as later this year, but our guess is it will be next year. The tadacept data is coming out also And this then announcing going into Phase I with our second program also will be next year. And hopefully, by the end of next year, we'll have Phase I data as well. And you've got your Phase II ATEX. And our Phase II ATEX trial yes. Oh, my god. How can I forget that? Second fourth quarter probably well, our guidance is 2026. Go on clinical trials. Was hoping by I'm at a conference next year. It may be a little early. We'll see. We'll see how recruitment goes. It's been an amazing year, and I know the future is going to be very successful for you. Our team has done a great job of executing. Yes. Thank you very much. Thank you for having Thank you.