AVROBIO, Inc. hosted a panel of investigators managing the patient experience in the Phase 2 FAB-GT clinical trial of AVR-RD-01, an investigational one-time gene therapy for Fabry disease, at the 14thInternational Congress of Inborn Errors of Metabolism (ICIEM), Nov. 21-23, 2021, in Sydney, Australia. Other presentations included updated safety data from the first lentiviral gene therapy clinical trials for Fabry disease and Gaucher disease type 1, as well as 10- to 12-month safety data from gene therapy-treated mice with mucopolysaccharidosis type II (MPSII), or Hunter syndrome. Nine patients have been dosed in the FAB-GT clinical trial to date, all of them in Australia. While the first three patients were treated using an academic vector and melphalan as a conditioning agent, the other six patients were treated using AVROBIO?s proprietary plato? gene therapy platform, which includes a lentiviral vector, a personalized busulfan conditioning regimen designed to implement precision dosing and an automated, closed manufacturing process intended to deliver potent and consistent drug product from manufacturing sites worldwide at commercial scale. Phase 1 and Phase 2 studies for Fabry disease Safety data from the first eight adult patients dosed in the Phase 2 FAB-GT trial (mean, range post-gene therapy follow-up: 16, 5-41 months) and the five adult patients dosed in the investigator-sponsored Phase 1 trial (mean, range post-gene therapy follow-up: 39, 33-58 months) show no adverse events (AEs) or serious adverse events (SAEs) related to drug product AVR-RD-01. AEs and SAEs experienced by trial participants to date have been generally consistent with myeloablative conditioning, protocol-mandated drugs, underlying disease or pre-existing conditions. Eleven SAEs (nausea, vomiting, dehydration, fever, febrile neutropenia and mucosal inflammation) were reported; all resolved without clinical sequelae. Safety data from a ninth patient recently dosed in the FAB-GT study are still being analyzed, but preliminary data are consistent with the overall safety profile. Previously reported efficacy data from the two trials have documented stable and sustained enzyme activity and reductions of 87% and 100% in kidney Gb3 inclusions for the evaluable kidney biopsies of two Fabry disease patients. AVROBIO is planning to share updated efficacy data from both trials during the first quarter of 2022. The safety data cut-off date for the Phase 1 trial was July 26, 2021, and for the FAB-GT trial was Aug. 20, 2021. Enrollment in the FAB-GT trial (NCT03454893) is ongoing, and further details are available on clinicaltrials The Guard1 study for Gaucher disease type 1: Safety data from the first patient dosed in the first in-human, open-label, multinational Phase 1/2 study of AVR-RD-02 (treated using AVROBIO?s proprietary plato? gene therapy platform) show no SAEs and no AEs to date related to drug product 14 months post-treatment. AEs reported for this patient have been consistent with myeloablative conditioning, protocol-mandated drugs, underlying disease and pre-existing conditions. This patient discontinued ERT one month before the gene therapy infusion and remains off ERT. Previously reported efficacy data for this patient indicates improvement across relevant biomarkers of Gaucher disease type 1. Platelet and hemoglobin concentration levels were maintained in the normal range. A second patient has been dosed in the clinical trial. Preclinical data for Hunter syndrome; Current clinical treatments for Hunter syndrome include ERT and hematopoietic stem cell (HSC) transplant, but neither is efficacious at treating neurological symptoms due to deficiencies in enzyme expression. Published preclinical research by the team at The University of Manchester in mice has demonstrated that lentiviral gene therapy with an optimized, proprietary tag can cross the blood-brain barrier and has the potential to deliver the functional enzyme (iduronate 2-sulfatase, or I2S) to the CNS. Preclinical evidence shows that, compared to untreated Hunter mice, Hunter mice treated with genetically modified HSCs at 10-12 months post-gene therapy have supra-physiological levels of I2S enzyme activity in the bone marrow, plasma and spleen (among other tissues and organs) and increased I2S enzyme activity levels in the brain, with no unexpected safety events to date. AVROBIO plans to initiate an investigator-sponsored Phase 1/2 clinical trial of AVR-RD-05 in Hunter syndrome in the second half of 2022. AVROBIO announced an exclusive, worldwide license agreement with The University of Manchester for this investigational lentiviral gene therapy in 2020.