Rare Daily Staff
Spruce Biosciences, which had been focused on endocrinology until the failure of its lead program in congenital adrenal hyperplasia in 2024, is seeking to remake itself with the acquisition of an experimental enzyme replacement therapy to treat Sanfilippo syndrome type B, a rare lysosomal storage disorder.
The experimental therapy, which BioMarin Pharmaceutical had been developing until selling it off in 2019 to Allievex, was subsequently acquired by Spruce after Allievex filed for bankruptcy in 2023. As part of its purchase, Spruce will be responsible for paying BioMarin up to $122.5 million in milestone fees and royalties on worldwide net sales in the high single digits to low teens.
Spruce expects to apply for approval for the therapy, tralesinidase alfa (TA-ERT), in the first half of 2026.
“This is truly a transformative moment for Spruce as we focus our expertise in rare disease on a potential near-term commercial opportunity with TA-ERT in MPS IIIB,” said Javier Szwarcberg, CEO of Spruce. “This new strategy opens a new chapter in our mission to provide transformative and life-changing therapies to patients affected by serious conditions with significant unmet medical need.”
Sanfilippo syndrome type B, or mucopolysaccharidosis IIIB, is caused by a deficiency in the enzyme alpha-N-acetyglucosaminidase (NAGLU), one of the four enzymes required for heparan sulfate degradation. The first symptoms generally appear between the ages of two and six years and consist of behavior disorders, intellectual deterioration, sleep disorders, and, in some cases, mild dysmorphism. With time, neurological involvement becomes more prominent with progressive loss of motor milestones and communication problems. The prognosis is poor, with death occurring in most cases in the late teens or early 20s.
Tralesinidase alfa is an investigational enzyme replacement therapy using a novel fusion of recombinant human alpha-N-acetyglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor 2 for the treatment of Sanfilippo syndrome type B or MPS IIIB. It is designed to restore NAGLU activity in the brain, and is delivered directly to the fluid surrounding the brain by an intracerebroventricular infusion. TA-ERT has received fast-track designation, rare pediatric disease designation, and orphan drug designation in the U.S. and EU. Spruce intends to submit the BLA of TA-ERT for the treatment of MPS IIIB in the first half of 2026.
TA-ERT has been shown to normalize cerebral spinal fluid heparan sulfate non-reducing end (HS-NRE) levels significantly and durably over a five-year period. Spruce said that in a March 2024 meeting with the FDA, the agency confirmed that HS-NRE is deemed to be a surrogate biomarker reasonably likely to predict clinical benefit and could serve as a basis for accelerated approval. The FDA also confirmed that the completed clinical and non-clinical studies of TA-ERT were sufficient for a BLA submission and provided guidance around key design elements of a confirmatory trial, which must be initiated prior to potential accelerated approval of TA-ERT.
Spruce said it will seek accelerated approval of TA-ERT for MPS IIIB based on existing non-clinical and clinical data approval and maximize the U.S. commercial potential of TA-ERT for treating MPS IIIB. Spruce will be required to conduct a confirmatory trial as a condition of accelerated approval. If the therapy is approved, Spruce said it will build a highly specialized commercial and medical affairs organization to support the commercialization of TA-ERT.
The company intends to establish its own commercial organization in the United States, the European Union, and the United Kingdom. It will also seek regional strategic collaborations and a network of third-party distributors in other international markets.
As of December 31, 2024, Spruce had cash and cash equivalents of $38.8 million. The company expects its cash runway to fund its current operating plan through the end of 2025.
photo: Javier Szwarcberg, CEO of Spruce Biosciences
Stay Connected
Sign up for updates straight to your inbox.