Tectonic Therapeutic, Inc. Common Stock Stifel 2026 Virtual Cardiometabolic Forum

Well, obviously we've got two programs in the clinic, and actually there's things behind that as well, which we don't spend a lot of time talking about. Lead program is relaxin, and as you know, we're in phase II in a randomized study in Group 2 pulmonary hypertension with preserved ejection fraction heart failure, and we've got a readout from that study coming in the next couple of months. We are really getting close there. We've also got a single arm phase II study in PH-ILD. Our second program is our TX2100 program, which is an antagonist to APJ for hereditary hemorrhagic telangiectasia. We just had our phase I readout, which was really safe, very well tolerated. We had a very clean preclinical tox package, and I would say the data to date in the normal healthy volunteers mirrors what we saw preclinically.

We'll be moving forward into a phase I-B, hopefully by the end of the year, in patients who require hematologic support, so really some of the most severe patients, as well as a phase II randomized dose-ranging study in early 2027. Very high level, hopefully. I'm sure we'll get into a lot more detail on both programs.

It really was, because no one's ever taken an APJ antagonist into the clinic and into normal healthy volunteers.

One of the questions, if you look at the preclinical data, people said, "Oh, are you going to get the hypertension that you get associated with the VEGF inhibitor?" We absolutely saw no signs of that. It was really very well tolerated. I get asked if we had a biomarker.

The good news about this target, as you said, is it's selective. It also tends to be quiescent.

It's hard to find a biomarker in normal healthy volunteers. It gets upregulated in patients. But we did have a biomarker in that we had TMDD.

which can be used as a surrogate for receptor occupancy. It's a really strong signal that you're binding the receptor. By looking at inferred receptor occupancy levels, we could then say, "Okay, what are the exposures we're going to want to get to in patients?" That was one way we looked at that. That got us to exposure X.

Then we said, "Okay, now looking at the HHT preclinical models, which tend to translate to the clinic, based on that, what exposures do we think we need to get to?" Two orthogonal ways, they sent us to the same place, which gives us confidence in the target exposures that we're going after in the phase I-B and the phase II study.

I don't want to get ahead of myself, and I think what you have to understand is there's been so little research in this area. There's not a lot to go on. In the setting of moderate to severe epistaxis, which is moderate to severe nosebleeds, which many of these patients have, and these aren't the nosebleeds that are associated- like we think about schoolmates having when we were in grade school.

By the way, some of those who kept having them probably had HHT. The disease gets worse as you get older, but these can really be severe nosebleeds that really impact a patient's quality of life.

There's one validated measure of that. It's called the ESS score, the Epistaxis Severity Score.