Hey, everyone. Good morning and welcome to day three of the 2025 Bank of America Healthcare Conference. Thanks for joining this session with Tectonic Therapeutic. My name is Alex Stranahan. I'm Senior Biotech Analyst at Bank of America, and I'm pleased to introduce Alise Reicin, President and CEO of Tectonic. She'll be running through some slides and going over the company. With that, Alise, over to you.
Good morning. This slide is our standard disclaimer language. I'm going to spend the next 15 minutes for those of you in the room who don't know Tectonic, just giving you a high-level overview. At Tectonic, we're leading the way in the discovery and development of GPCR -targeted biologics. The company was founded in 2019 by Tim Springer and Andrew Kruse, and we went public via reverse merger in June 2024. We have an unusually experienced and successful leadership team. Between us, we've led teams that have resulted in over 20 first approvals for drugs across a variety of therapeutic areas, which enables us to be TA-agnostic and therefore choose targets that we think have the highest probability of success.
The focus today is going to be on our long-acting relaxin program, for which we are now in phase II with highly supportive phase I -B data, and I will show you some of that today. The initial indication for our relaxin program is group 2 pulmonary hypertension associated with preserved ejection fraction left-sided heart failure. I'll refer to that sometimes as PH-HFpEF. We are emphasizing a subpopulation called CPCPH that I'll talk about in a few slides. Our phase I -A in normal healthy volunteers confirmed the safety of the molecule and also suggests that we have a potential best-in-class molecule. The phase I -B results we think increase the probability of success for our ongoing phase II.
We considered multiple indications for it, including HFpEF, which is an indication Lilly actually went into, but we chose what we did because we think that the benefits are likely to be highest in this subpopulation of CPCPH patients with group 2 PH. Furthermore, PH-HFpEF is a very large underserved patient population, over a million patients in the U.S. alone, high five-year mortality, and no approved therapies, making it what we believe to be a multi-billion dollar opportunity. We're not alone as AstraZeneca is exploring both PH-HFpEF as well as pulmonary hypertension associated with HFrEF, reduced ejection fraction heart failure, also known as PH-HFrEF. We, in fact, recently expanded our phase I-B into PH-HFrEF. If we go into that as well, it'll almost double the patient population.
I'm not going to spend time today talking about our TX-2100 program, but it's targeting hereditary hemorrhagic telangiectasia, HHT, the second most common bleeding disorder occurring in about 70,000-75,000 patients in the U.S., and again, a population for which there is no approved therapy. We've demonstrated efficacy in a preclinical model, which has shown translation to the clinic. Lastly, we are well capitalized after a recent raise with over $300 million in cash and a runway into fourth quarter of 2028. In terms of pipeline-related catalysts and the relaxin program, we'll have data from part B of our phase I-B study in PH-HFrEF later this year, and we'll have phase II data in 2026. For the 2100 program, we just started our IND -enabling studies.
We should be in the clinic later this year or early next year with efficacy studies starting about a year later. Switching first to the disease, pulmonary hypertension associated with left heart failure has two subtypes: IPCPH and CPCPH. IPCPH is isolated post-capillary pulmonary hypertension. You have elevated pressures on the left side of the heart because of heart failure, and those pressures backflow into the pulmonary circulation, leading over time to failure of the right side of the heart because it is pumping out against higher pressures, and that eventually is what kills the patients. Their pulmonary vasculature is normal. However, patients with combined pre- and post-capillary pulmonary hypertension, CPCPH, have both that left-sided heart pressures that backflow into the pulmonary circulation. Their pulmonary vasculature, however, is not normal. Their pulmonary circulation starts to look like they have PAH.
They get a narrowing of the lumen of the pulmonary vessels, and as you're trying to send the same amount of blood through that smaller lumen, you get an increase in the pulmonary vascular resistance, PVR, and that's how you differentiate them from IPCPH. Importantly, in our phase II, we're going to enrich for CPCPH, who we think may have the greatest benefit from relaxin because their exercise capacity is limited both by their heart failure as well as by that high pulmonary vascular resistance, which prevents enough blood from getting into the left side of the heart. The epidemiology is shown on the left side of this slide. HFpEF in the U.S. is about 4 million patients. About 1.4 million of those have PH-HFpEF.
Depending on whether you define CPCPH as PVR greater than two wood units or PVR greater than three, you can see the range of the number of patients. As I said, if we go into group two, PH-HFrEF will almost double the patient population. We believe relaxin has multiple different effects, all of which should be beneficial in this patient population. First, it is a vasodilator, both in pulmonary and systemic circulation, which should decrease afterload, making it easier for the right and left side of the heart to pump blood out and to function. relaxin also has lusitropic effects, meaning that it actively relaxes the left ventricle during diastole, which should improve the diastolic dysfunction of preserved ejection fraction heart failure, which does not adequately relax or fill with blood during diastole.
This might be especially important in patients with CPCPH, as if you can reduce the pulmonary vascular resistance by the vasodilation, you should increase the amount of blood that goes into the heart from the pulmonary circulation during diastole. If you've also enabled that left heart to relax during diastole, the heart can take that blood in and then pump it out during exercise. relaxin also has antifibrotic and remodeling effects of both the pulmonary vessels as well as the left heart via upregulation of metalloproteases as well as inhibition of TGF-β. With long-term therapy, we think this could be quite important. The phase I -B data I'm going to show you today is from the one and only interim analysis we did.
That study is now, that part A of the study is now complete, and the final data is actually going to be shown this weekend at the ESC Heart Failure Meeting in Belgrade. The data I'm going to show you today is from 16 out of the 19 patients. In the phase I -B study, patients get admitted to the unit, they get a right-heart cath, and hemodynamics are done at baseline. We do hemodynamics over the next eight hours. We average those after they've gotten a single dose of relaxin. We pre-specified that for a drug to work in PH-HFpEF, it would need to demonstrate both an improvement in left heart function and pulmonary hemodynamics. We successfully demonstrated this in our phase I -B study where we met or exceeded our goals.
What you see here is both the change from baseline and the % change from baseline, and in the brackets are the 95% confidence intervals. Just to remind you, if a 95% confidence interval excludes zero, it means it's statistically significant, and all of these were statistically significant. The first row you can see is pulmonary capillary wedge pressure. It's measuring pressure in the left atrium. It's a great measure of left heart function, and you can see that TX45 treatment resulted in an 18% decrease, demonstrating clear improvement in left heart function. We pre-specified we wanted to see a 15%-20% decrease in the CPCPH population in pulmonary vascular resistance, PVR, because that's where it's elevated. In fact, we exceeded that, seeing a 32%-35% decrease whether you define CPCPH as PVR greater than two or greater than three.
We were also really pleased to see that we saw close to an 18% improvement in cardiac output, which should bode well for the need to include increased cardiac output during exercise. That was driven by a change in stroke volume, not heart rate, which is exactly what you want to see. We also decreased TPR, total pulmonary resistance, by 26%. That is the pressure that the right heart is pumping against. Bringing that down in the population by 26% can only be good for patients. Of course, pulmonary hypertension is defined by an elevated pulmonary pressure, and we reduced that as well. Importantly, on this slide, what you can see in that first column is that at baseline, as PVR increases, cardiac output decreases. It is lower in that CPCPH patient.
Importantly, treatment with relaxin increased cardiac output more in those patients with higher PVR, again, going along with our CPCPH hypothesis. The drug was well tolerated, no SAEs, immunogenicity. The most common AE was fatigue, which was not drug-related. It was transient. It lasted three hours. It only happened on the first day of treatment after a very long day in the lab. It was gone by the next day when drug levels were still high. 6MWT is going to be the approval endpoint, and so everybody wants to know how do these hemodynamics translate to that. There is not a lot of literature in group 2 PH. We do know that decreasing wedge pressure in these patients alone should improve exercise capacity to some extent. A 20% decrease has been associated with about a 20-meter increase in 6MWT.
We really think that in CPCPH, by improving both PVR and cardiac output, you sort of get more bang for the buck. Where in one study in CPCPH, where you decrease the wedge by that same 20%, but you also decrease the PVR by 30%, you got almost a 70-meter increase in 6MWT. Now, that's not our target for our program. This was a very, very high PVR patient population, but it gives you a sense of why we think you'd get added benefits. TX45 is well tolerated. We showed both an improvement in left heart function as well as improved pulmonary hemodynamics, and we think the data supports our enrichment strategy for CPCPH. Looking ahead, this is the design of our phase II study, right-heart cath at baseline.
Patients are randomized to one of three treatment arms, 300 Q2 or 300 Q4 of our drug or placebo, and then right-heart cath at the end. PVR in the PVR greater than three population is the primary endpoint, a secondary endpoint looking at the overall population, and we're looking at 6MWT in addition. Coming to the end, there is we do have competition. AstraZeneca is in this space, both with an Fc fusion as well as with an oral. Our half-life is double what their half-life is. We're testing both Q4 week and Q2 week. We think Q4 week will be our dose. They're only testing Q2 week. Their phase II is also in group 2 PH, but they're including both, as I said, HFpEF and HFrEF with a PVR in the overall population as their primary endpoint.
Just in conclusion, we're positioned to deliver on value-creating milestones. We have two pipeline candidates addressing untapped markets with significant market potential, and we have a steady cadence of inflection points in 2025 and 2026 and a proven leadership team that's well capitalized to execute with a very strong balance sheet. I think I was told I got to keep it right to 15 minutes, and so I'm happy to take any questions as the next group comes in. Thank you.