Orchard Therapeutics plc announced data from an ongoing proof-of-concept clinical trial evaluating the safety and efficacy of OTL-203, a gene therapy for the treatment of mucopolysaccharidosis type I (MPS-I) developed at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan. The results presented in an oral presentation at the Society for the Study of Inborn Errors of Metabolism (SSIEM) symposium include up to 12 months of follow-up for the first patient treated. As of the date of last follow-up, six patients with the severe Hurler subtype of MPS-I have been treated with the cryopreserved formulation of OTL-203 gene therapy. All treated patients were followed for a minimum of two months, with the longest follow-up extending out to 12 months. At the time of treatment, patients ranged in age from 14 months to 35 months. Five out of six patients had previously been treated with enzyme replacement therapy (ERT) and discontinued ERT treatment three weeks prior to enrollment, consistent with trial protocol. The primary endpoints of the trial are safety, hematological engraftment by day 45 following treatment and preliminary efficacy as measured by IDUA enzyme activity (up to supraphysiologic levels) at one-year post-treatment. Treatment with OTL-203 demonstrated: Gene therapy and the selected conditioning regime were well-tolerated. Rapid hematologic reconstitution, with neutrophil and platelet engraftment within three weeks following treatment. Engraftment in the bone marrow and periphery by assessment of the vector copy number. Supranormal IDUA enzyme expression in peripheral blood, with the first patient treated achieving levels 10 times above the normal range and stable over time up to 12 months post gene therapy. Key secondary and exploratory endpoints include normalization of urinary glycosaminoglycans (GAGs), growth velocity and effects on motor and cognitive function at one- and two-years post-treatment. For the first two treated patients, with 12 months and six months of follow-up, respectively: Rapid metabolic correction of GAG levels in the urine and cerebrospinal fluid was observed, reflecting restoration of IDUA enzyme expression in the periphery and in the central nervous system. For the patient with 12 months of follow-up: Preliminary clinical evaluation showed signs of resumed growth, improved motor skills and a stable cognitive score.