Lexeo Therapeutics Maps Gene Therapy Milestones, Eyes Key 2027 Readout

Key Points

• LX2006: Lexeo has begun its registrational SUNRISE-FA 2 study for Friedreich’s ataxia cardiomyopathy, with top-line data expected in the second half of 2027 and a planned biologics license application in the first half of 2028.
• LX2020: Updated Phase I/II data for PKP2-associated arrhythmogenic cardiomyopathy are expected in the fourth quarter, including 12-month results from most high-dose patients and a regulatory update on whether NSVT can serve as a pivotal-study endpoint.
• Financial position: Lexeo reported more than $230 million in cash at the end of the second quarter and expects its mid- to high-$20 million quarterly burn rate to provide runway into 2028, supporting development and planned regulatory filings.

Lexeo Therapeutics NASDAQ: LXEO outlined upcoming clinical and regulatory milestones for its gene therapy programs in Friedreich’s ataxia cardiomyopathy and PKP2-associated arrhythmogenic cardiomyopathy during the Chardan Healthcare Conference.

Chief Financial Officer Lou Tamayo said the clinical-stage company is focused on genetically mediated diseases with high unmet need. Its lead candidate, LX2006, is being evaluated for Friedreich’s ataxia cardiomyopathy, while LX2020 is in a Phase I/II study for PKP2-associated arrhythmogenic cardiomyopathy.

Friedreich’s Ataxia Program

Lexeo began enrolling a registrational study of LX2006, called SUNRISE-FA 2, at the end of the second quarter, Tamayo said. The company expects a top-line readout from the Phase III study in the second half of 2027 and plans for a biologics license application filing in the first half of 2028.

According to Tamayo, earlier Phase I/II data showed effects on left ventricular mass index, multiple biomarkers and the modified Friedreich’s Ataxia Rating Scale, or mFARS. He said LX2006 appears to affect components of the neurological disease associated with the peripheral nervous system, including skeletal muscle and dorsal root ganglia, but does not transduce the brain.

Lexeo recently acquired Mantle Therapeutics to add neurologically focused Friedreich’s ataxia programs to its pipeline. Tamayo said the strategic goal is to develop a therapy that can reach the brain and potentially be used in cohorts previously treated with LX2006.

“Ultimately, there’s a potential there to have a therapeutic package that treats both the cardiac side, where we know LX2006 is showing a good effect, but also to have a component that reaches the brain to treat the totality of FA,” Tamayo said.

The company’s CLARITY-FA natural-history study is serving as a feeder study for SUNRISE-FA 2. Tamayo said Lexeo had activated 19 sites across eight countries and enrolled 22 patients. The pivotal study is seeking 13 treated patients and 13 untreated control patients, he said. Patients in CLARITY-FA may transition into the treatment study if they meet neutralizing-antibody and site-activation requirements.

PKP2 Cardiomyopathy Data Expected in Fourth Quarter

Lexeo expects to report updated LX2020 data in the fourth quarter, including results from most high-dose patients with at least 12 months of follow-up, alongside a regulatory update.

Chief Medical Officer Narinder Bhalla said the company’s January update showed a 14% reduction in premature ventricular contractions, or PVCs, and a 22% reduction in non-sustained ventricular tachycardia, or NSVT. Among two patients with nine months of follow-up, Lexeo reported a 65% reduction in NSVT, according to Bhalla.

Bhalla said NSVT is the more clinically meaningful measure because it can influence decisions involving implantable cardioverter-defibrillators, anti-arrhythmic drugs and patient monitoring. He said the company would look for a deepening reduction in arrhythmia burden over time, with 12 months representing an important initial point for evaluating response.

Lexeo has not yet disclosed whether the U.S. Food and Drug Administration would accept NSVT as a pivotal-study endpoint. Bhalla said the company’s discussions with the agency are continuing and that Lexeo hopes to provide more direction in its upcoming update.

Tamayo noted that Lexeo received Regenerative Medicine Advanced Therapy designation in August. He said the package supporting that designation included more contemporary data than the data previously shared in the first quarter and was centered substantially around NSVT.

• Lexeo has identified NSVT and PVC burden as key measures in the LX2020 program.
• Bhalla said reductions of roughly 35% to 40% could compare favorably with effects associated with currently used anti-arrhythmic medicines, which he characterized as being in the 20% to 30% range.
• The company has also seen an increase in right ventricular ejection fraction in one patient, though Bhalla said structural changes may take longer to emerge.

Safety and Financial Runway

Bhalla said the LX2020 program continues to use steroids and sirolimus for immunosuppression, with no change to the protocol. He said liver-enzyme elevations observed at the 6.0E13 dose were managed within protocol-defined measures, and no patients required hospitalization or additional medications beyond the designated regimen.

On financing, Tamayo said Lexeo had slightly more than $230 million in cash at the end of the second quarter. The company expects quarterly cash burn in the mid- to high-$20 million range, which it said provides operating runway into 2028.

Tamayo said the company expects its cash resources to support operations through the planned LX2006 biologics license application filing, as well as chemistry, manufacturing and controls work. Lexeo is already manufacturing at commercial scale and is making commercial, market-access and medical-affairs hires, he said.

About Lexeo Therapeutics (NASDAQ:LXEO)

Lexeo Therapeutics, Inc is a clinical-stage biotechnology company developing genetic medicines for genetically defined cardiovascular and central nervous system diseases. The company uses adeno-associated virus (AAV) gene-delivery technologies to develop treatments intended to address the underlying causes of disease rather than only manage symptoms.

Lexeo's pipeline includes investigational programs for conditions such as Friedreich ataxia-associated cardiomyopathy, a serious heart complication of Friedreich ataxia, and genetic forms of neurodegenerative disease.

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