Lexeo Therapeutics, Inc. Common Stock Stifel 2026 Virtual Cardiometabolic Forum

Sure We will do Q&A.

Thanks, Paul. It is great to be here. Just some background. Lexeo is a clinical stage genetic medicines company. Our lead program is focused in Friedreich's ataxia, and as Paul mentioned, we have added additional preclinical programs to the pipeline, which I will spend some time talking about on the FA side. We are also working in a set of genetic cardiomyopathies. The lead program on that side is a gene therapy focused on PKP2 arrhythmogenic cardiomyopathy, which is the most common genetic cause of life-threatening arrhythmias in arrhythmogenic cardiomyopathy. The company is about seven years old, and we have moved into a pivotal study for our Friedreich's ataxia program, and we will be reading our data for our PKP2 arrhythmogenic cardiomyopathy program later this year. As Paul mentioned, we recently completed an acquisition, a small acquisition of a private clinical stage company.

This acquisition added several programs to our Friedreich's ataxia pipeline that are all focused on introducing frataxin into the brain. This is a complementary approach to our current clinical stage program, which is focused on the cardiovascular component of Friedreich's ataxia. We believe that the two together could meaningfully improve the standard of care in this disease. While LX2006, our FA cardiomyopathy program, is likely to be the standard of care for treating the cardiovascular disease, we believe that there are other approaches that can allow us to address the neurologic side of the disease through this expanded pipeline. Excited to spend more time talking about this today, both the FA programs and our PKP2 arrhythmogenic cardiomyopathy program.

Maybe, Nadi, you could speak to the- Sure the population we are focused on and then the enrollment into CLARITY-FA.

Yeah. I will start with the CLARITY-FA enrollment. Paul, as you mentioned, it is the natural history study that has the same inclusion criteria as our pivotal study, and we are recruiting well into that study, from the standpoint of we are at about 20 plus, and two others that are kind of eligible and just waiting. All of these patients are eligible to come into the pivotal trial, provided that their neutralizing antibodies and total antibody counts are fine. They could enter into the pivotal trial. The pivotal trial is focused on a cohort of patients that have a left ventricular mass index that is greater or equal to 2 standard deviations from the mean. That is where we are focusing on, given the fact that this is the population that as you look at LVMI, and particularly this type of population, there is a significant risk of increased mortality.

For every 10% change in LVMI, you have almost a 20% increase in risk of mortality. We feel that that is the population that, given also our phase I, phase II data, we feel that we should be concentrating on to show a very meaningful, clinically meaningful effect size and go from there. That's kind of where we are right now with our CLARITY enrollment and the pivotal focus on the population.

Let me just punctuate- Great a few points there.

As Nadi mentioned, 22 patients. Our registrational study is a total of 26 patients in the adult cohort. I'd note that the sites where we have the patients enrolled in the natural history study are the same sites that will ultimately be treatment sites as well. It's a matter of operational steps to move the patients from one study to the other, with the caveat of the existence of neutralizing antibodies would obviously be a factor that makes the patients ineligible for the treatment study and that rate of neutralizing antibodies we've seen roughly consistent with prior literature and prior experiences at about 15% or thereabouts.

Yeah, sure. So we powered it at a 15% effect size from the baseline, and the trial is the 26 patients is 13 and 13. Thirteen in an untreated arm, 13 in a treated arm. The comparator is the change from baseline in the treatment arm versus the untreated arm. The 15% threshold was really arrived upon for a couple of reasons. One, we want to make sure 10% reduction is, as I mentioned earlier, is that clinical bar and the regulators have agreed that that's a clinically meaningful reduction. The 15% was really a threshold that we arrived on for a couple of reasons. One was we wanted to beat that 10% bar and be really clinically meaningful and be in an unquestionable range of effect size, and 15% gives us that.

When we look at also our phase I, phase II data, and we look at the patients who were in the higher two doses and how they progressed at six months, we know that the effect size we saw there was about 28%. So we feel that given that that 15% is we should be able to reach that given our phase I, phase II data, and the fact that we beat that 15% pretty handily in the phase I, phase II data. So that's the rationale for powering it where it is. It also, the couple of other offshoots are that it allows us to get to a reasonable sample size, and also complete the trial in a reasonable amount of time.