Lexeo Therapeutics acquires Mantle Therapeutics and adds four Friedreich ataxia programs while advancing CNS gene therapy collaborations and LX2006.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Lexeo Therapeutics is expanding its Friedreich ataxia (FA) development strategy beyond systemic gene therapy through the acquisition of Mantle Therapeutics and three research collaborations focused on increasing or replacing frataxin in the brain. The transactions add four programs spanning small-molecule, protein-replacement and antisense oligonucleotide approaches, while Lexeo continues enrollment in the pivotal SUNRISE-FA 2 study (NCT07721025) of LX2006.
Mantle acquisition adds four therapeutic approaches
Under the agreement, Lexeo will acquire Mantle, a clinical-stage company developing therapies for FA. The transaction includes LX3010 (MTL-104), an oral combination therapy that combines HDAC inhibition with NRF2 pathway modulation to increase frataxin expression and address mitochondrial dysfunction and oxidative stress.
Early clinical data from 11 patients showed an approximately six-point improvement in modified Friedreich Ataxia Rating Scale (mFARS) scores after 16 weeks, alongside a mean nine-fold increase in frataxin protein levels from baseline in muscle biopsies. These findings are early-stage and will require confirmation in larger controlled studies.
The acquisition also brings three earlier-stage programs. LX3030 (MTL-707) is an oral, tissue-penetrant benzamide HDAC inhibitor intended to increase endogenous frataxin production in the central nervous system. Preclinical studies have shown increased frataxin levels.
LX3050 (MTL-501) is a recombinant human frataxin protein fused to an anti-transferrin receptor 1 (TfR1) Fab. The approach uses TfR1-mediated transport to facilitate delivery across the blood-brain barrier. In vitro studies showed dose-dependent improvements in measures of mitochondrial function.
LX3070 (MTL-801) is a discovery-stage antisense oligonucleotide-Fab conjugate that targets FXN mRNA stabilization to increase endogenous frataxin translation. The program also uses an anti-TfR1 Fab to support CNS delivery.
Sequential CNS dosing could complement LX2006
Lexeo is also investigating whether patients who receive systemic LX2006 could later receive additional frataxin gene therapy targeting the CNS, particularly the cerebellum, which plays a central role in FA-associated neurological dysfunction.
A collaboration with Weill Cornell Medicine will evaluate intra-cisternal administration of LX2006 after systemic dosing in large-animal models. Researchers will assess dosing parameters and immunosuppression strategies relevant to repeat administration.
Lexeo has separately secured an option agreement with Vivet Therapeutics for VTX-PID, an IgG-degrading enzyme that could support repeat AAV administration by reducing antibody-mediated barriers.
An option agreement with Apertura Gene Therapy provides access to a novel intravenously administered blood-brain barrier-crossing capsid. The approach could provide a less invasive route for subsequent CNS delivery following initial systemic LX2006 treatment.
LX2006 remains the lead clinical priority
Despite the expanded pipeline, Lexeo said enrollment in the SUNRISE-FA 2 pivotal study remains its highest operational and capital-allocation priority. The study is evaluating LX2006, the company’s frataxin gene therapy program, in patients with FA-associated cardiomyopathy.
Topline results remain expected in the second half of 2027. Lexeo has previously positioned LX2006 as a potential disease-modifying treatment for the cardiac manifestations of FA, although its clinical benefit will depend on the results of the pivotal study.
Following the Mantle transaction, Lexeo plans to assess the acquired programs against scientific, clinical, strategic and financial criteria. The company expects to identify a priority program in early 2027 and submit an investigational new drug application for its next FA development candidate during 2027.
Transaction expands FA strategy while preserving cash runway
Lexeo will pay Mantle shareholders $8.3 million upfront, through a combination of cash and equity, with up to $13 million in additional milestone payments. The potential total consideration is therefore $21.3 million.
The company said its existing cash runway remains projected into 2028, including funding to advance one acquired program into clinical development. Future investment will be tied to predefined milestones as Lexeo evaluates which approaches can most effectively address the neurological component of FA.
The expanded portfolio gives Lexeo multiple strategies for restoring frataxin in the brain, including increasing endogenous production, replacing the missing protein and stabilizing FXN messenger RNA. The company also plans to evaluate these approaches both independently and alongside prior LX2006 treatment, potentially establishing a sequential treatment framework for the multisystem disease.
Reference
Lexeo Therapeutics Enters into Agreement to Acquire Mantle Therapeutics and Announces Multiple New Strategic Collaborations to Expand Leadership in Friedreich Ataxia, Lexeo Therapeutics, 22 September 2026
Study of LX2006 Gene Therapy in Friedreich Ataxia Cardiomyopathy (SUNRISE-FA 2), ClinicalTrials.gov ID NCT07721025
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.