Lexeo Therapeutics is a New York City-based clinical-stage genetic medicine company dedicated to transforming healthcare by applying pioneering science to fundamentally change how disease is treated.
What were the key findings you released earlier this year regarding your Alzheimer’s gene therapy?
Our approach targets the genetics behind Alzheimer’s rather than downstream mechanisms. The APOE2 gene is associated with a significantly lower risk of Alzheimer’s onset and slower disease progression. Most individuals have the APOE3 gene, which confers a normal risk of Alzheimer’s. For the ~2% of the population that are APOE4 homozygotes (with two copies of the APOE4 allele), this risk of disease development increases 15-fold.
Our therapy, LX1001, delivers the APOE2 allele to the central nervous system of APOE4 homozygotes to impart this protective effect. In our trials, we observed a dose-dependent increase in APOE2 expression, particularly in the highest dose cohort, and reductions in tau biomarkers—associated in literature with cognitive decline—in participants with moderate disease. Notably, we achieved these results without any instances of amyloid-related imaging abnormalities (ARIA), a serious side effect linked to amyloid antibody treatments. This unique safety profile makes our approach compelling for further exploration.
In terms of your objectives, do you foresee this genetic approach arresting Alzheimer’s entirely? How does it compare to other treatments targeting amyloid plaques?
While the LX001 data is promising, it’s too early to say if we can completely halt Alzheimer’s progression. Current therapies typically slow cognitive decline rather than stop it. Our Phase 1/2 study focused on safety and biomarker impact, showing significant tau reduction in moderate patients without ARIA. Future studies will require larger, controlled trials to assess cognitive outcomes. Comparatively, existing amyloid treatments often cause ARIA, particularly in APOE4 homozygotes, with up to 40% experiencing symptoms. Our gene therapy avoids ARIA, offering a precision medicine approach tailored to high-risk APOE4 patients, potentially addressing unmet needs without the risks seen in amyloid therapies.
Let’s discuss Lexeo’s cardiovascular applications. You mentioned positive results in that area too—could you elaborate?
We are advancing gene therapies for genetic cardiovascular diseases, notably Friedrich's ataxia (FA), addressing its cardiac pathology. Mid-year data revealed successful frataxin gene expression in cardiac biopsies, reducing hypertrophy—the hallmark of this condition measured via left ventricular mass index or LVMI—by about 11%, exceeding the clinically meaningful threshold of 10%. This reduction, alongside lower troponin levels (a marker of cardiac cell death) and lateral wall thickness, suggests a tangible impact on disease progression. With fewer than ten precision cardiovascular treatments available today, we see immense potential in bringing genetic medicines to this underpenetrated field.
Why focus on cardiovascular diseases and Alzheimer’s specifically? These seem like distinct areas.
While the connection may not seem obvious, both areas lack precision medicine solutions. In cardiovascular care, regulatory agencies historically favored large, longer mortality outcome studies, limiting the introduction of precision treatments. Alzheimer’s faces a similar issue; current therapies are one-size-fits-all, despite genotype-specific responses. We see an opportunity for precision gene therapies in both fields. Operationally, both require scalable vector manufacturing, and we have developed a platform capable of supporting large indications like cardiovascular and Alzheimer’s diseases. This infrastructure enables us to address significant gaps in both treatment landscapes effectively.
How would you assess Lexeo’s first year on NASDAQ and your approach to navigating today’s challenging funding environment?
After our IPO, we completed another public financing in March 2024, extending our cash runway into 2027. This positions us to fully advance our pipeline, with major cardiac program readouts expected in 2025. Positive clinical results will underpin our next financing round, likely extending our runway further. For public companies, success hinges on completing trial enrollments, generating impactful readouts, and translating those into funding opportunities. We aim to swiftly transition our programs into pivotal studies and eventually to market approval, keeping investor confidence high.
Where do you hope to see Lexeo Therapeutics by the end of next year?
By the end of 2025, we aim to have significant data readouts for our cardiovascular programs, establishing a clear path from Phase 1/2 to pivotal studies. Ideally, at least one pivotal trial will have commenced. On the Alzheimer’s front, we expect to progress through a partnership with a company experienced in central nervous system diseases, leveraging their capabilities to advance our gene therapy. Our long-term focus remains cardiovascular diseases, while partnering in Alzheimer’s allows us to scale efficiently while optimizing resources.
In the Alzheimer’s space, our approach is unique, targeting the high-risk APOE4 homozygote population, which still faces unmet needs. Collaborating with a company active in Alzheimer’s could enhance complementarity between our AD portfolio and existing treatments, leveraging infrastructure and combining strengths to deliver comprehensive patient care. This approach aligns with our mission to introduce impactful precision medicines in underpenetrated areas.
