BioMarin Pharmaceutical Inc. has selected a new drug development candidate, BMN 250, a novel fusion of alpha-N-acetyglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor 2 (IGF2), for the treatment of Sanfilippo B syndrome or Mucopolysaccharidosis type IIIB (MPS IIIB). BioMarin has initiated IND-enabling studies and expects to initiate clinical studies with BMN 250 in mid-2015.

Discovered by BioMarin, BMN 250 is an enzyme replacement therapy using recombinant human NAGLU with an IGF2, or Glycosylation Independent Lysosomal Targeting (GILT) tag. BMRN 250 is delivered directly to the brain using BioMarin's patented technology. BioMarin has issued patents which broadly cover delivery of lysosomal enzymes directly into the cerebrospinal fluid to treat lysosomal storage diseases.

"We are pleased to add an exciting new candidate to our pipeline that could be a potentially first-in-class therapy for Sanfilippo B patients who currently have no drug treatment options available," said Jean-Jacques Bienaimé, chief executive officer of BioMarin. "Developing BMN 250 for Sanfilippo B or MPS IIIB brings together the best of BioMarin's scientific and clinical expertise. We are building upon a deep knowledge of MPS diseases, and experience developing fusion proteins and enzyme replacement therapies overall. Adding a fourth treatment for MPS complements our current franchise of two approved therapies for the treatment of MPS I and MPS VI and a third expected for MPS IVA."

Data on the NAGLU fusion protein will be presented at the Lysosomal Disease Network's (LDN) 10th Annual WORLDSymposium being held February 11-13 in San Diego, California.

"We are encouraged by the results in the preclinical data where we have seen excellent cellular uptake of the enzyme throughout the brain," said Elizabeth Neufeld, Ph.D., Emerita Member, Brain Research Institute and Professor Emerita, Biological Chemistry, David Geffen School of Medicine at the University of California Los Angeles. "The animal studies show intracellular storage is cleared with NAGLU-IGF2 treatment which we hope will translate well in the clinic."

Mucopolysaccharidosis type IIIB (MPS IIIB) or Sanfilippo B syndrome is a lysosomal storage disease belonging to the group of mucopolysaccharidosis and characterized by severe and rapid intellectual deterioration. MPS IIIB is caused by deficiency in the enzyme alpha-N-acetylglucosaminidase (NAGLU), one of the four enzymes required for heparan sulfate (HS) degradation. There are an estimated 1,000 - 2,000 patients in the developed world with Sanfilippo B syndrome. The first symptoms appear between the ages of two and six years old, with behavior disorders, intellectual deterioration, sleep disorders and very mild dysmorphism. The neurological involvement becomes more prominent around the age of ten with loss of motor milestones and communication problems. Seizures often occur after the age of ten. The prognosis is poor with death occurring in most cases of type IIIB between 30-40 years of age.

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions.