disease and plasma GL-3 levels is not well understood [2]. Studies have also shown that a deacylated form of GL-3, glo- botriaosylsphingosine (Lyso-GL-3), is also elevated in patient plasma and could correlate better with disease manifestation [3]. We recently developed and validated a novel liquid chromatograph- tandem mass spectrometry (LC-MS/MS) based method to simulta- neously quantify both GL-3 and Lyso-GL-3 in human plasma samples. The method incorporates a single-phase extraction system to eliminate the need for solvent exchange prior to LC-MS/MS analysis. This novel multiplex approach significantly improves inter-assay bias between GL-3 and Lyso-GL-3 assays as well as assay turnaround time. References: 1) Aerts et. al. Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies. J Inherit Metab Dis. 2011 Jun;34(3):605-19. 2) Lobato et. al. Biomarkers in Lysosomal Storage Diseases. Diseases. 2016 Dec 4(4): 40. 3) Rombach et. al. Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease. Biochim Biophys Acta. 2010 Sep;1802(9):741-8. doi:10.1016/j.ymgme.2018.12.082 67 ICV-administered tralesinidase alfa (BMN 250 NAGLU-IGF2) is well-tolerated and reduces heparan sulfate accumulation in the CNS of subjects with Sanfilippo syndrome type B (MPS IIIB) Maureen Cleary a , Nicole Muschol b , Maria Luz Couce c , Paul Harmatz d , Joy Lee e , Shuan-Pei Lin f , Ilyas Okur g , Fatih Ezgu g , Heidi Peters e , Martha Solano Villarreal h , Adam J. Shaywitz i , Heather Cahan i , Anita Grover i , Andrew Melton i , Lynn Smith i , Stephen M. Maricich i , Maria J. de Castro Lopez c , a Great Ormond Street Hospital, London, United Kingdom, b University Medical Center Hamburg-Eppendorf, Hamburg, Germany, c Hospital Clínico Universitario de Santiago, A Coruña, Spain, d UCSF Benioff Children’s Hospital Oakland, Oakland, CA, United States, e Royal Children’s Hospital, Melbourne, Australia, f Mackay Memorial Hospital, Taipei, Taiwan, g Gazi University Hospital, Ankara, Turkey, h Universidad del Rosario, Bogota, Colombia, i BioMarin Pharmaceutical Inc., Novato, CA, United States Sanfilippo Syndrome type B (MPS IIIB) is a lysosomal storage disorder caused by deficiency of the α-N-acetylglucosaminidase (NAGLU) enzyme and subsequent heparan sulfate (HS) accumu- lation in the brain. Sanfilippo B patients display progressive neurocognitive decline and typically do not live past the second or third decades of life. Tralesinidase alfa (BMN 250 NAGLU-IGF2) is a novel enzyme replacement therapy (ERT) for Sanfilippo B consisting of NAGLU enzyme fused to insulin-like-growth factor 2 (IGF2) to enhance lysosomal targeting. This report presents preliminary results from the first human study of tralesinidase alfa (NCT02754076). NCT02754076 is a phase 1/2, open-label study with two parts. Part 1 consisted of 3 dose-escalation periods (≥4 weeks) of intracerebroventricular (ICV) tralesinidase alfa administered as a weekly isovolumetric bolus infusion. Subjects from Part 1 and from an ongoing observational study of Sanfilippo B patients (NCT02493998) continue to Part 2, a 48-week treatment period to examine efficacy/safety at the maximum tolerated tested dose (300 mg). For enrollment into Part 1, 1-10 year old subjects with Sanfilippo B must have deficient NAGLU activity at screening. Cerebrospinal fluid (CSF) total HS levels show sustained normalization after 1-3 weeks of tralesinidase alfa treatment in 7/7 treated subjects. Abdominal MRI imaging demonstrates that liver and spleen volumes normalize after 24 weeks of treatment in 9/9 and 7/9 subjects, respectively. Stabilization in developmental quotient (DQ) was observed in 5/ 7 treated subjects. Safety data indicate that ICV-administered tralesinidase alfa is generally well-tolerated. These findings demonstrate that tralesinidase alfa can be safely administered into brain ventricles via isovolumetric bolus infusion and that this treatment approach leads to a marked pharmacodynamic re- sponse in the CNS and visceral organs of Sanfilippo B patients. doi:10.1016/j.ymgme.2018.12.083 68 Safety and efficacy of advanced and targeted acid α-glucosidase (AT-GAA) (ATB200/AT2221) in ERT-switch nonambulatory pa- tients with Pompe disease: preliminary results from the ATB200- 02 trial Paula R. Clemens a , Tahseen Mozaffar b , Benedikt Schoser c , Drago Bratkovic d , Barry J. Byrne e , Ozlem Goker-Alpan f , Mark Roberts g , Peter Schwenkreis h , Kumaraswamy Sivakumar i , Ans T. van der Ploeg j , Jacquelyn Wright k , Sheela Sitaraman k , Jay A. Barth k , Hjalmar Lagast k , Priya Kishnani l , Xue Ming m , a University of Pittsburgh and Department of Veterans Affairs Medical Center, Pittsburgh, PA, United States, b University of California, Irvine, CA, United States, c Friedrich-Baur-Institut, Neurologische Klinik, Ludwig- Maximilians-Universität München, Munich, Germany, d PARC Re- search Clinic, Royal Adelaide Hospital, Adelaide, SA, Australia, e University of Florida, Gainesville, FL, United States, f O&O Alpan LLC, Fairfax, VA, United States, g Salford Royal NHS Foundation Trust, Salford, United Kingdom, h Neurologische Klinik und Poliklinik des Berufsgenossenschaftlichen, Universitätklinikum Bergmannsheil, Bo- chum, Germany, i Neuromuscular Research Center, Phoenix, AZ, United States, j Erasmus Medical Center, Rotterdam, Netherlands, k Amicus Therapeutics, Inc., Cranbury, NJ, United States, l Duke University Medical Center, Durham, NC, United States, m Rutgers New Jersey Medical School, Newark, NJ, United States Late-onset Pompe disease (LOPD) is a rare, inherited mul- tisystemic metabolic disorder characterized by progressive muscle weakness and respiratory impairment that can result in patients losing the ability to walk. Currently, recombinant human acid α- glucosidase (GAA) enzyme replacement therapy (rhGAA ERT alglucosidase alfa) is the only FDA-approved treatment. AT-GAA (ATB200/AT2221), a next-generation rhGAA ERT/pharmacological chaperone regimen, is being evaluated for adults with LOPD in a first-in-human, open-label, phase 1/2 trial ATB200-02 (NCT02675465). The study enrolled 20 patients in 3 cohorts: ERT- switch ambulatory (n=11), ERT-switch nonambulatory (wheel- chair-bound and unable to walk unassisted) (n=4), and ERT-naive ambulatory (n=5). This analysis evaluates the 12-month interim data for the ERT-switch nonambulatory patients, including safety assessments, muscle strength test for upper limbs, pulmonary function tests, and patient-reported outcomes. Mean GAA protein exposure (protein and activity) was higher with AT2221 coadmin- istration. Increases in upper extremity strength, assessed by quantitative and manual muscle testing, were observed at months 6 and 12. Reductions from baseline in muscle enzymes (CK, ALT, AST) and disease substrate (urine Hex4) were observed and S40 Abstracts / Molecular Genetics and Metabolism 126 (2019) S17–S156