Spruce Biosciences is a clinical-stage biopharmaceutical company developing therapies for rare neurological disorders. Its lead program, Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT), targets Mucopolysaccharidosis Type IIIB (MPS IIIB), also known as Sanfilippo Syndrome Type B — an ultra-rare, fatal pediatric disease with no approved treatments. MPS IIIB is caused by a deficiency of the enzyme NAGLU, which leads to toxic accumulation of heparan sulfate in the brain, progressive neurodegeneration, and death typically by the mid-to-late teens. TA-ERT is a fusion protein delivered directly into cerebrospinal fluid via an implanted device, bypassing the blood-brain barrier to restore enzyme activity and slow neurological decline. Clinical data across 22 patients show TA-ERT normalized heparan sulfate levels in nearly all patients within six months, with cognitive stabilization relative to untreated patients. The FDA has accepted heparan sulfate as a surrogate biomarker supporting accelerated approval, and Spruce plans to file a BLA in Q4 2026. The addressable U.S. patient population is roughly 135 patients. If approved, Spruce would sell TA-ERT at a high per-patient price point consistent with other orphan enzyme replacement therapies, using a small commercial team of five to ten people. Spruce licenses the TA-ERT intellectual property from BioMarin and manufactures through contract manufacturers. The company has two earlier-stage programs — an anti-CRH antibody for congenital adrenal hyperplasia and a CRF1 antagonist for major depressive disorder, the latter recently discontinued after a safety signal.