Lexeo Therapeutics is on a mission to transform the field of gene therapy, moving beyond treatments for rare diseases to make life-changing therapies available for widespread conditions like Alzheimer’s disease and genetically defined heart diseases known as cardiomyopathies.
Founded in 2019, Lexeo is a Cure Collaboration Residency company, with CEO Nolan Townsend and scientific pioneer Ron Crystal, MD, leading the charge to expand gene therapy’s reach and impact to redefine the possibilities of genetic medicine.
The notion of gene therapy — giving a one-time treatment to someone with a rare disease with a specific targetable mutation — extends back decades. After years of research conducted across the industry, the FDA just approved the first gene therapies for sickle cell disease in December 2023, and other treatments are under evaluation for other rare conditions.
But Townsend and Crystal,Chair of the Department of Genetic Medicine at Weill Cornell Medicine, have faith that gene therapy can be scaled up and provided at a more reasonable cost to thousands if not millions of people with more common diseases.
Founded in 2019, Lexeo Therapeutics is a Collaboration Residency company at Cure. "Nolan took the idea of gene therapy one step further and believed that at some point, this technology is going to be used in a larger patient population," said José Manuel (Manny) Otero, PhD, Chief Technical Officer at Lexeo.
"We're innovating not just on the diseases we're targeting and the genetic modifications we're making, but also in terms of manufacturing and how we run clinical studies,” Otero explained. “We believe that gene therapy is no longer just for ultra-rare diseases. It could be a transformative, curative medicine for diseases in very large populations that currently have no treatment."
Thinking Like a Vaccine Company
Scalability is Lexeo's main differentiator from others in the field. The company has a manufacturing process and commercialization and clinical operations teams designed to function at that scale.
Its pipeline features novel capsid-based gene therapies designed to treat homozygous APOE4-associated Alzheimer’s disease as well as cardiomyopathies such as Friedrich's ataxia cardiomyopathy, arrhythmogenic cardiomyopathy, desmoplakin cardiomyopathy and hypertrophic cardiomyopathy.
"The numbers of people affected by cardiomyopathies or other mechanisms of heart failure, as well as Alzheimer's disease, are very large populations," explained Otero.
To treat so many patients, Lexeo chose to think big. And that means thinking like a vaccine company — something Otero has experience with, having worked on many different modalities and vaccines, including, the Gardasil HPV vaccine, before he began working at Lexeo in May 2024.
"To manufacture our viruses, we use a rather unique insect cell culture baculovirus expression system. This system was originally designed to be used in vaccine manufacturing and is attractive because of its scalability and robustness," Otero explained. "Lexeo has always thought about long-term manufacturing. Rather than thinking like a traditional gene therapy company, they were thinking more like a vaccine company. That means the product has to be low cost, highly distributed and highly scalable, with robust manufacturing platforms."
That's a position the company has taken from day one. Clinical trial and drug development take years, and process changes made late in the game to lower costs and increase scalability can require a company to return to the clinical trials stage to prove that these changes do not affect a treatment's safety or efficacy — a lengthy and expensive endeavor.
"If you're going to target larger populations, you have to have a general framework from the beginning to generate a product at a reasonable cost and scale to reach many patients," said Otero. "Your manufacturing process, your distribution process, your engagement with clinical sites and how you operate a clinical trial machine must be constructed with that intent. That's how we have thought at Lexeo from day one."
Thriving in Cure’s New York City Life Sciences Ecosystem
The Lexeo team is delighted to be at Cure. "We made a decision early on that we need to be able to innovate and run the manufacturing process ourselves. We need to be able to develop our processes and transfer them to manufacturing partners," said Otero. "We need the ability to troubleshoot and pivot very quickly or try new things. And we're able to do that in the lab that we built at Cure. When we tell people that we're running fully controlled bioreactors and doing purification and analytical development on the 6th floor of a building on Park Avenue in Manhattan, people look at us a little funny. But that's what's happening.
"We've chosen to be a New York City-based biotech company, and I think that is relatively rare," he continued. "The scientists and engineers we have working here love being in New York City. Many of our investors, advisors, legal team and banking team are New York-based. There's a natural fit with those other ecosystems that makes the collective that much more effective. I'm a New Yorker by birth, so maybe I'm also biased — but there's just something magical about being here."