Lexeo Therapeutics, Inc. Common Stock 2026 Global Healthcare Conference

Yeah. Lexeo is a genetic medicines company primarily focused on two diseases. One is Friedreich's ataxia, the second is arrhythmogenic cardiomyopathy, and specifically the PKP2 mutation. The company was a spin-out originally from the genetic medicine lab at Weill Cornell Medicine here in New York. We acquired another gene therapy company in 2021 that was focused on genetic cardiovascular disease, and those two components of the pipeline have come together to the company that you know today. Our most advanced program, as I mentioned, is treating Friedreich's ataxia. We're focused primarily on the cardiovascular component of the disease, which is the cause of death for up to 70% of Friedreich's ataxia patients. We're also seeing a clinically meaningful improvement in the neurologic component of the disease. We evaluate this through the mFARS scale, which is the endpoint used to approve the current commercially available treatment.

We're seeing about a 2.5 to 3-point improvement on the mFARS scale, and this effect size appears to be deepening over time. We have patients out to 24 months of treatment follow-up that are seeing persistent benefit. On the cardiac side, we are reversing the hallmark of the disease, which is cardiac hypertrophy, and we're achieving the effect size on mFARS of the neurologic scale that I mentioned. We believe the two together would be a step change in the standard of care for the treatment of Friedreich's ataxia. This is a program that's now in a registrational study. We're working towards a top-line readout in the second half of next year. We're excited about this as our most advanced program. The next program, as you mentioned, is treating arrhythmogenic cardiomyopathy. I think this is a very interesting indication.

I'd say, frankly, it's under the radar today. This is a 60,000-patient rare disease in the U.S. it's, for example, more than twice the size of Duchenne muscular dystrophy, making it one of, if not the largest, commercial opportunity in systemically administered gene therapy today. We have a phase I study that's completed enrollment. As you mentioned, we'll have a readout of this study towards the end of the year. This will focus on our high dose, where we'll have most, if not all of the patients at 12 months of treatment follow-up. We'll also have a regulatory update in the same time period, which will give a lens into the path forward into the next study, which we hope to be an approval study. That one's moving rapidly as well.

I think, obviously PKP2 is the nearest term clinical data readout regulatory update that we have. But FA is very important to our strategy, and we'll have the top-line readout in 2027.

Yeah. The hallmark of this disease is hypertrophy or thickening of the heart wall. We measured that via a cardiac MRI endpoint called left ventricular mass index. We achieved a left ventricular mass index reduction of 28% in our phase I study at the six-month time point. The effect size that we need to achieve in our registrational study at the same time point is 15%. I would even say that 28% we achieved in the phase I is understated because we had one patient for which we utilized their three-month value instead of six-month because at their clinical site, there was a hurricane, so they weren't eligible or able to go for their six-month visit. But if you look at nine months, that patient had achieved a 30% reduction.

The point I'm making is a 28% clears the 15% threshold very credibly, but it's also probably understated relative to what the true effect size would have been at six months. That's the primary endpoint, the endpoint on which the study has been powered. We have secondary endpoints in the trial of troponin, for which we saw about a 60% reduction in troponin in the phase I. We have mFARS, which is the neurologic scale. I mentioned the effect size earlier. Then we have the Kansas City Cardiomyopathy Questionnaire, which is another cardiac functional scale. I think all are important endpoints for the disease. The effect size that we've achieved on LVMI, we think makes the primary endpoint a slam dunk for us in terms of achieving that.

The other aspect is we have an ongoing natural history study, CLARITY-FA, which it serves as, in a way, a feeder into the treatment study. We have a picture of the patient baselines in CLARITY-FA. So we know that the overall disease burden in terms of LVMI that's likely to end up into the treatment study is one that would allow us to credibly achieve the endpoint as well. I think from a lot of different vantage points, we have a high degree of confidence in our ability to deliver against the 15% improvement and see some very clinically meaningful improvements in some of the secondary endpoints as well.

Right. Are you actually randomizing too?

There is a random allocation of patients into the untreated control or into the treatment arm. This was designed to ensure that there was balance in the patient phenotypes across the treatment arm and the untreated control. We want to ensure roughly similar levels of disease burden across those two arms of the study to ensure that we're comparing the apples to apples in terms of the patient populations.