Lexeo snaps up Stelios, bolstering pipeline with trio of rare heart disease gene therapies

As Lexeo Therapeutics ushers two gene therapies toward the clinic, the company is adding another three heart disease programs to its already busy pipeline. The assets come through Lexeo’s acquisition of Stelios Therapeutics, which was founded on research out of the University of California, San Diego. 

The company declined to disclose financial details. 

Through the deal, Lexeo gets its hands on a gene therapy for hypertrophic cardiomyopathy and two treatments for arrhythmogenic right ventricular cardiomyopathy. Both are inherited diseases of the heart muscle. The former, also called HCM, causes the muscle walls of the heart to thicken, potentially to the point where they can obstruct blood flow, while the latter, ARVC, causes the muscular wall of the heart to break down over time, which can cause an abnormal heartbeat and sudden death. 

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Lexeo is developing the HCM program for patients whose disease stems from mutations in the TNNI3 gene, which codes for a protein found in heart muscle cells. The company estimates that patients with a TNNI3 mutation comprise between 5% and 7% of the total patients with HCM, who number around 650,000 in the U.S. 

There are no approved treatments for HCM, though the FDA expects to decide on Bristol Myers Squibb’s myosin inhibitor mavacamten for the treatment of obstructive HCM in January 2022. Cytokinetics recently reported phase 2 data for its own myosin inhibitor in HCM, while BioMarin and Tenaya Therapeutics are both working on gene therapies targeting MYBPC3 and DWORF mutations, respectively. 

Of Lexeo’s new ARVC programs, one delivers the gene that codes for Plakophilin-2 (PKP2), which represents about 70% of patients, said Lexeo CEO Nolan Townsend. The other program delivers the gene that codes for the connexin 43 protein. 

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Lexeo launched in January with $85 million and 18 programs primarily developed at Weill Cornell Medicine. It plans to move one of those, a treatment for Batten disease, into a pivotal trial in 2022, Townsend said. 

Another program, a treatment for Alzheimer's disease, is in a phase 1 study in people with the APOE4 gene, a variant known to increase the risk of developing the disease. Following close behind is a treatment for cardiomyopathy linked to Friedreich’s ataxia, which causes progressive nervous system damage and movement problems. The company aims to get this program into the clinic by the end of the year, Townsend said. 

“In the time frame in which the Friedreich’s ataxia cardiomyopathy program is reaching clinical proof of concept, we could expect to have one or perhaps two of these preclinical programs [from Stelios] entering the clinic,” Townsend said. 

Lexeo’s 15 preclinical programs remain under wraps. 

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Though Lexeo’s first programs are for rare diseases, it has a broader vision to bring gene therapy beyond the likes of Duchenne muscular dystrophy and hemophilia and into more common diseases. HCM and ARVC are both rare heart diseases, but they are on “the larger end for rare diseases,” Townsend said. Building the capacity to develop and manufacture gene therapies for the tens of thousands of patients with these ailments would be a steppingstone toward the ability to treat many more patients with more prevalent conditions. 

And, with the advent of genetic testing for heart disease, it may turn out that HCM and ARVC are more common than previously thought. 

“There have not been many genetics-based cardiac diseases that have an existing therapy,” Townsend, adding that the first one was Pfizer’s Vyndaqel (tafamidis) for cardiomyopathy stemming from transthyretin amyloidosis. 

“Not until this product was launched did cardiologists have access to genetic testing. They would see rare forms of cardiomyopathy, believing they were more common cardiac diseases, which led to rare cardiac disease being underdiagnosed or misdiagnosed,” Townsend said. 

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With Vyndaqel on the market and the anticipated launch of BMS’ mavacamten, Townsend reckons that genetic testing will be available to cardiologists more broadly. 

“Through these means, we may see the prevalence of these cardiac diseases could be a lot larger than the existing literature suggests,” he said.