Lexeo Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thanks for having us. Thanks for having us.

Sure. I'll start. Lexeo is a genetic medicines company primarily focused on cardiovascular disease. Our most advanced program is treating Friedreich's ataxia. Here, we're focused on the cardiac pathology of the disease. We're also seeing an improvement in the neurologic component of the disease. Our next most advanced program is treating plakophilin-2 or arrhythmogenic cardiomyopathy. This is the most common genetic mutation causing arrhythmogenic cardiomyopathy. There are about 60,000 patients in the U.S. with this disease, making it one of the largest opportunities in clinical stage gene therapy. Here we have a phase I study that we've completed enrollment, and we're working towards a data readout later this year associated with this program. I think we'll probably spend most of the time talking about those programs, but we have other earlier programs in cardiovascular disease as well.

Maybe, Nani, to ask you to speak to that.

Yeah, sure. A lot of efforts underway. Certainly, we've been working a lot with our societies and making sure that we're educating through those channels. You mentioned the social media. That's a big part of our education portfolio as well. Then engaging with thought leaders wherever we can to make sure that when they are having their conversations or when they're on the podium, that they're talking through the importance of the cardiac impact of this disease. Then using the advocacy organizations as well. Definitely more work to be done. I think that this whole thing of trying to coordinate care between the various specialties that manage these patients is absolutely critical, and we continue to make sure that these patients are diagnosed early from a cardiac perspective and then are being followed. So that's really where the emphasis has been through all those channels.

We've had great engagement on the social side as well, actually.

I would add, I think the introduction of a treatment for the cardiovascular disease will necessarily lead to more cardiologists engaging. We see this typically in rare diseases when there is no treatment. It's difficult to engage a population of physicians because they would say, "Well, even if I diagnose this disease, what can I do to treat the patients?" I think the introduction of a therapy will change that paradigm. I would draw a corollary to amyloid, where there was polyneuropathy and then cardiomyopathy second, and first there were neurologists involved, and cardiovascular physicians became involved later, and I think we'll see a similar pattern here as well.

Maybe you can talk about LVMI.

Yeah, sure. LVMI is a hallmark of the disease. All these patients who go on to having their cardiac disease, the first thing is this thickening of the heart walls and left ventricular hypertrophy, so the LVMI goes up. This is a classic hallmark of the disease that they go through this phase. If you look at the population under natural history conditions, again, not a lot of published data out there on the natural history. But looking at the data sets that we have been privy to, there's very negligible change over a year in these patients, no more than 3%-5%. We don't expect a lot of change in the study that we're looking at, which is a six-month duration.

But LVMI and the marker of that as these patients, as we've shown in our earlier data, that as they get treated, we see the LVMI come down towards normal. Definitely an important parameter, and there's data that also links it to mortality risk. We know that every 10 unit increase in left ventricular mass index portends a 20% increased risk in mortality for these patients. All in all, a hallmark of the disease and a key predictor of mortality in these patients.

We chose LVMI also just because of how precise the measurement technique is. There's very limited inter user variability. As Nani said, you typically see this increasing in LVMI over time via the pathology of the disease as a couple percent increase per year. It's an endpoint that very precise, very objective. We don't expect to see spontaneous improvements in LVMI, and we've not seen that across any other cardiac disease.