Announcement • Jun 09
Spruce Biosciences Announces Long-Term Tralesinidase Alfa Enzyme Replacement Therapy Data in Sanfilippo Syndrome Type B (MPS IIIB) Presented at the 18th International MPS Symposium
Spruce Biosciences announced that data demonstrating the long-term benefit of tralesinidase alfa enzyme replacement therapy (TA-ERT) in patients with Sanfilippo Syndrome Type B (MPS IIIB) were presented at the 18th International MPS & Related Lysosomal Diseases Symposium, which took place June 4-7, 2026 in Florence, Italy. The data show that long-term administration of TA-ERT resulted in rapid and durable reduction of heparan sulfate and preserved cognitive and non-cognitive outcomes relative to natural history patients. In an analysis of 22 patients who enrolled in interventional studies of TA-ERT with follow-up of up to six years, TA-ERT treatment: Rapidly and durably normalized levels of cerebral spinal fluid heparan sulfate non-reducing end (CSF HS-NRE), a surrogate endpoint reasonably likely to predict clinical benefit in patients with MPS IIIB; Stabilized cognitive function, as assessed by the Bayley-III Cognitive Raw Score (BSID-C), the cognitive subscale of the validated Bayley Scales of Infant and Toddler Development – Third Edition (Bayley-III), relative to declines seen in untreated natural history patients; Stabilized receptive and expressive communication, as well as fine and gross motor skills, compared with a decline in these outcomes in untreated natural history patients, as assessed by the Vineland Adaptive Behavior Scales – Second Edition (VABS-II); Stabilized cortical gray matter volume, which declined in untreated natural history patients, and normalized liver and spleen volume; and Was generally consistent with the safety profile of intracerebroventricular (ICV) administration; over the six-year study, approximately 6,000 doses were administered to 22 patients. Sanfilippo Syndrome Type B (MPS IIIB) is an ultra-rare, serious, and fatal genetic disease characterized by deficiency in N-Acetyl-Alpha-Glycosaminidase (NAGLU), an enzyme required for the catabolism of heparan sulfate (HS) in lysosomes. The accumulation of toxic levels of cerebral spinal fluid heparan sulfate in the brain is the underlying pathophysiology of MPS IIIB. Although signs and symptoms of MPS IIIB can vary amongst affected individuals, progressive neurodegeneration typically follows a predictable path to brain atrophy, cognitive and developmental impairment, hyperactivity with aggressive and destructive behavior, delayed speech, hearing loss, and motor skill deficits. Somatic manifestations include coarse facial features, hepatosplenomegaly, and gastrointestinal symptoms. The final stage of MPS IIIB is typically marked by severe dementia, loss of motor function, and seizure activity, with patients largely bed-ridden and requiring constant care, requiring feeding tubes for hydration and nutrition, and ultimately leading to death. The estimated life expectancy of individuals with MPS IIIB ranges from 15 to 19 years of age. Currently, there are no FDA-approved therapies for MPS IIIB, and management of the disease consists of limited palliative care to improve quality of life. Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT) is a fusion protein comprised of recombinant human alpha-N-acetylglucosaminidase (rhNAGLU). TA-ERT is intended as an enzyme replacement therapy for the treatment of patients with Sanfilippo Syndrome Type B (MPS IIIB) who lack rhNAGLU enzyme activity. TA-ERT is expected to restore rhNAGLU enzyme activity in the central nervous system following intracerebroventricular injection. rhNAGLU typically lacks the mannose-6 phosphate residues that are essential for efficient cellular uptake via the M6P receptor pathway. As a result, the naked enzyme is poorly absorbed by cells, including neurons. To address this challenge, TA-ERT is fused to an insulin-like growth factor 2 peptide, which binds to the cation-independent mannose-6-phosphate on cell surfaces. This fusion enables the enzyme to be internalized and delivered to the lysosome, thereby enhancing its therapeutic potential for treating MPS IIIB. By restoring NAGLU enzymatic activity and promoting clearance of lysosomal heparan sulfate and heparan sulfate non-reducing end in the brain, TA-ERT therapy is expected to preserve neuronal cell health and potentially halt or slow the neurological decline and improve clinical outcomes in affected patients. TA-ERT has been evaluated in three clinical studies in participants with MPS IIIB: the interventional study 201 and extension studies 202 and 401. TA-ERT has been administered to 22 individuals diagnosed with MPS IIIB, and has demonstrated an adequate safety profile based on integrated six years of safety data.
