CLN2 disease is a rare, fatal, pediatric neurogenetic disorder resulting from deficiencies in the tripeptidyl peptidase 1 (TPP1) protein. While bi-monthly infusions of recombinant human TPP1 (cerliponase alfa) to the brain has provided benefit to patients, a global survey of patients and caregivers indicated that >90% believe there is a need for alternative treatments, such as gene therapies, with greater efficacy and without the need for biweekly administration. Latus Bio, Inc. has developed an AAV-based gene therapy using a novel capsid variant, AAV-Ep+, delivering the hTPP1 transgene. In animal studies, AAV-Ep+ robustly transduces ependymal cells lining CNS ventricular spaces as well as intraparenchymal neurons, allowing for production and secretion of TPP1 protein into the CSF and brain parenchyma. Preclinical studies in Cln2-/- mice and NHPs support LTS-101 as a treatment for CLN2 disease. In Cln2-/- mice, bilateral ICV administration of LTS-101 demonstrates high transduction, expression, engagement and LTS-101 produces TPP1 protein throughout the brain and reduces lysosomal protein accumulation (lipofuscin). In NHPs, bilateral ICV administration of LTS-101 produces brain-wide TPP1 activity, high and durable levels of TPP1 in the CSF, a favorable safety profile, and low systemic exposure. LTS-101 is manufacturable at 250L scale, producing high quality drug product at suitable concentrations for clinical testing. Clinical development planning is progressing in collaboration with world-leaders in CLN2 disease. LTS-101 is a promising gene therapy candidate with the potential to treat CLN2 Batten disease patients with a one-time ICV administration providing stable, long-term expression of TPP1 while eliminating the caregiver and patient burden of repeated ERT treatments.