R. Nolan Townsend, MBA, an industry veteran in pharma finance, shared a vision for the future of gene therapy with Ronald Crystal, MD, a pioneer in the field, and together they founded LEXEO Therapeutics in 2020. LEXEO’s clinical-stage programs focus on genetic cardiovascular diseases and Alzheimer’s, working to bring precision genetic medicines to patients in these therapeutic areas.
Townsend recently discussed LEXEO’s programs and the landscape of gene therapy clinical trials, approvals and reimbursement.
Cure: Let’s talk about the disease areas LEXEO is working on. Where do you stand clinically with cardiovascular and Alzheimer’s, and what are you excited about?
Townsend: Our focus in genetic cardiovascular diseases is led by a program treating the cardiac pathology of a disease called Friedreich’s ataxia. We're currently in a Phase 1/2 study for this indication and into our second dose cohort. We're expecting to have a clinical data readout this year, which will give some very interesting insights into the impact that we're having on patients behind that program. We also have a program treating arrhythmogenic cardiomyopathy, for which we expect to be in the clinic soon.
For Alzheimer’s, we have a program focused on APOE4 homozygous Alzheimer's disease, and here we're delivering the APOE2 gene to the central nervous system of APOE4 homozygotes. We're currently in a Phase 1/2 study for this indication. We read out low-dose data associated with this program at an Alzheimer's conference recently, and we showed reduction in some of the key biomarkers commonly associated with Alzheimer's disease. So, I think the early data is very interesting.
Cure: Alzheimer’s disease has been a sort of final frontier in terms of solving not only the disease and treatment but also delaying and preventing it. What do you think about the recently approved Leqembi®?
Townsend: It's an exciting time for treatments in this disease area. Leqembi® was an important milestone for the Alzheimer's field. What's interesting about this and other therapies utilizing a similar mechanism is that they have shown clinical benefit.
Underneath the data for this program is another very interesting trend — patients of different genotypes respond differently to the therapy. There’s a gene called APOE. People who are APOE4, which is the subset we're focused on, have a higher risk, and they respond differently to this therapy than APOE3s do. APOE2s respond differently than APOE4s as well. What that means to us is that precision medicine is likely to play an important role in the Alzheimer's field. We have a precision medicine in the form of a gene therapy targeting the APOE4 population. We think there remains a substantial unmet need even though there is now a treatment that exists for these patients.
Cure: Let's say somebody knows that they are predisposed to Alzheimer's because they have taken a genetic test. How likely is it that they will sign up for a clinical trial?
Townsend: A lot of families that inherit the APOE4 gene will see a number of members develop Alzheimer's disease, their grandmother or their aunt, their uncle, and so on. In those cases, individuals are often motivated to consider clinical trials, whether it's for preventative therapy or for a treatment, because they are thinking about their children. There is that inherent motivation to ensure that a therapy or preventative therapy exists because of the rest of their family that could benefit from it.
In the type of work we are doing in Alzheimer's disease, first, we're developing gene therapy for patients who have developed symptoms of Alzheimer's disease. But theoretically, it has a potential as a preventative treatment, which would mean that with a single administration of gene therapy, you could potentially delay or halt the progression of Alzheimer's disease. A single administration could ultimately change the profile of a patient with a high risk to that of a much lower risk. It's not a burdensome treatment course. It's a single administration in a 20-minute outpatient procedure.
Cure: Where do you see the cardiovascular field heading, and where do you see the role of gene therapy?
Townsend: I see the cardiovascular treatment landscape is where oncology was almost 15 years ago. There was a realization that one-size-fits-all treatments may not treat a very complex disease and that you need to break these diseases into their genetic components and then apply precision therapies. In our view, the cardiovascular treatment landscape will evolve in a lot of the same way. We will break these cardiovascular diseases into their genetic components and apply precision therapies to treat them. We have been advancing a pipeline of gene therapies aimed at treating these genetic cardiovascular diseases.
Cure: How do we tackle the reimbursement question?
Townsend: It's a challenging one, but I do see a light at the end of the tunnel. I'll give an example. A recently approved single-administration gene therapy for hemophilia B was priced at above $3 million, which is the most expensive medicine ever approved or commercialized in the world. But this medicine is replacing the current treatment for hemophilia B, which is a recombinant factor replacement that could cost the healthcare system every single year, for a single patient, between $600,000 and $800,000. If you take that $3 million price for a single administration, and you divide it by the annual treatment cost of the existing therapeutic option, and you look past year five, and for the rest of the patient's life, ultimately, this patient becomes a very low cost for the healthcare system. By treating these patients with gene therapy, you can almost move this disease off the balance sheet of the healthcare system. That's a very substantial change in how we would think about therapeutics in the future if we can completely offer functional cures to diseases. We could have diseases that society no longer needs to pay for.