tralesinidase alfa (AX 250) / BioMarin, Spruce Biosciences - LARVOL DELTA

Spruce Biosciences Receives U.S. FDA Breakthrough Therapy Designation for Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT) in Sanfilippo Syndrome Type B (MPS IIIB) (Businesswire) - "Biologics License Application Submission of TA-ERT for MPS IIIB Remains on Track for the First Quarter of 2026"

Breakthrough therapy • FDA filing • Genetic Disorders

Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice. (PubMed, Int J Mol Sci) - "Despite human trials of enzyme replacement therapy (ERT) (SBC-103, AX250) in MPS IIIB, there is currently no FDA approved treatment and a few palliative options. Here, we establish some osteogenic manifestations of MPS IIIB within the mouse model by radiographic and biomechanical tests, which are also differentially affected by age and sex. This suggests that some skeletal features of the MPS IIIB mouse model may be used as biomarkers of peripheral disease correction for preclinical treatment of MPS IIIB."

Journal • Preclinical • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys. (PubMed, Toxicol Rep) - "Correlations between TA concentrations in plasma and brain regions in direct contact with the cisterna magna suggest glymphatic drainage may be responsible for clearance of TA from the CNS. The data support the administration of TA by isovolumetric bolus ICV infusion to pediatric patients with MPS IIIB."

Journal • PK/PD data • CNS Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Ophthalmology • Pediatrics • IGF2

Safety, Tolerability and Efficacy of ICV AX 250 Treatment in MPS IIIB -OLE (clinicaltrials.gov) - P4 | N=15 | Enrolling by invitation | Sponsor: Allievex Corporation | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Hunter Syndrome • Lysosomal Storage Diseases

A phase 1/2 study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B. (PubMed, J Clin Invest) - P1/2 | "ICV administration of tralesinidase alfa effectively normalized HS and HS-NRE as a prerequisite for clinical efficacy. Peripheral drug exposure data suggests a role for the glymphatic system in altering tralesinidase alfa efficacy."

Journal • P1/2 data • CNS Disorders • Hepatology • Lysosomal Storage Diseases

Safety, Tolerability and Efficacy of ICV AX 250 Treatment in MPS IIIB -OLE (clinicaltrials.gov) - P4 | N=15 | Not yet recruiting | Sponsor: Allievex Corporation

New P4 trial • Hunter Syndrome • Lysosomal Storage Diseases

Tralesinidase alfa enzyme replacement therapy prevents disease manifestations in a canine model of mucopolysaccharidosis type IIIB. (PubMed, J Pharmacol Exp Ther) - "These findings demonstrate the ability of TA to prevent or limit the biochemical, pathological, and cognitive manifestations of canine MPS IIIB disease, thus providing support of its potential long-term tolerability and efficacy in MPS IIIB subjects. Significance Statement This work illustrates the efficacy and tolerability of tralesinidase alfa as a potential therapeutic for MPS IIIB patients by documenting that direct CNS administration to MPS IIIB dogs prevents accumulation of disease-associated GAGs in lysosomes, hepatomegaly, cerebellar atrophy, and cognitive decline."

Journal • Preclinical • Developmental Disorders • Hepatology • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases • IGF2

Biochemical evaluation of intracerebroventricular rhNAGLU-IGF2 enzyme replacement therapy in neonatal mice with Sanfilippo B syndrome. (PubMed, Mol Genet Metab) - "The overall therapeutic effects of single dose ICV-ERT with rhNAGLU-IGF2 in Naglu neonatal mice were long-lasting. These results suggest a potential benefit of early treatment, followed by less-frequent ICV-ERT dosing, in patients diagnosed with MPS IIIB."

Journal • Preclinical • IGF2

Translational studies of intravenous and intracerebroventricular routes of administration for CNS cellular biodistribution for BMN 250, an enzyme replacement therapy for the treatment of Sanfilippo type B. (PubMed, Drug Deliv Transl Res) - "Combined results from IV administration of BMN 250 in Naglu mice and IV and ICV administration in healthy juvenile non-human primates suggest a limitation to therapeutic benefit from IV administration because enzyme distribution is restricted to brain vascular endothelial cells: enzyme does not reach target neuronal cells following IV administration, and pharmacological response following IV administration is likely restricted to clearance of substrate in endothelial cells. In contrast, ICV administration enables central nervous system enzyme replacement with biodistribution to target cells."

Journal • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Differential Uptake of NAGLU-IGF2 and Unmodified NAGLU in Cellular Models of Sanfilippo Syndrome Type B. (PubMed, Mol Ther Methods Clin Dev) - "In contrast, under conditions of limited exposure duration, NAGLU-IGF2 was taken up more rapidly than the unmodified NAGLU into MPS IIIB primary fibroblasts, astrocytes, and cortical neurons, where it efficiently degraded accumulated HS. These studies illustrate the importance of using physiologically relevant conditions in the evaluation of enzyme replacement therapies in cellular models."

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