RegenxBio Enters Strategic Partnership with Nippon Shinyaku for MPS I and II Gene Therapies

Rare Daily Staff

RegenxBio has entered into a strategic partnership with Nippon Shinyaku to develop and commercialize gene therapies for the rare lysosomal storage disorders mucopolysaccharidosis II and mucopolysaccharidosis I.

Under the terms of the agreement, RegenxBio will receive $110 million at closing and up to an additional $700 million if certain milestones are achieved, consisting of $40 million in potential development and regulatory milestones and $660 million in potential sales milestones. RegenxBio will also receive double-digit royalties on net sales in the United States and Asia.

Nippon Shinyaku will commercialize both products in the Licensed Territory, and RegenxBio will lead future clinical development of RGX-121 and RGX-111. RegenxBio retains all rights to and 100 percent of any proceeds related to the sale of the Priority Review Voucher (PRV) for RGX-121 received upon potential approval.

RegenxBio will lead the manufacturing of both products for clinical and commercial supply in the Licensed Territory. RegenxBio reserves the right to develop and commercialize these products in countries outside of the Licensed Territory.
MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S), leading to an accumulation of glycosaminoglycans, including heparan sulfate in tissues that ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system. Early developmental milestones may be met in severe forms of the disease, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. There is currently no treatment to address fatal neuronopathic CNS disease in MPS II.

RGX-121 is an experimental gene therapy designed to deliver the iduronate-2-sulfatase gene (IDS) that encodes the iduronate-2-sulfatase enzyme (I2S) using the NAV AAV9 vector. RGX-121 expressed protein is structurally identical to normal I2S. RGX-121 is administered directly to the central nervous system (CNS) using intracisternal or intracerebroventricular delivery. Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS.

RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the FDA and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency.

MPS I is a rare autosomal recessive genetic disease caused by a deficiency in the lysosomal enzyme alpha-L-iduronidase (IDUA). This deficiency leads to an accumulation of glycosaminoglycans, including heparan sulfate, in tissues, which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system. This can include excessive fluid accumulation in the brain, spinal cord compression, and cognitive impairment.

Current disease modifying therapies for MPS I include hematopoietic stem cell transplant and enzyme replacement therapy with a recombinant form of human IDUA administered intravenously. However, intravenous enzyme therapy does not treat the CNS manifestations of MPS I, and hematopoietic stem cell transplant can be associated with clinically significant morbidity and mortality. Key biomarkers of IDUA enzymatic activity in MPS I patients include its substrate heparan sulfate, which has been shown to correlate with neurocognitive manifestations of the disorder.

RegenxBio’s RGX-111 is an experimental gene therapy designed to use the AAV9 vector to deliver the α-l-iduronidase (IDUA) gene to the central nervous system. Delivery of the IDUA gene within the cells in the central nervous system could provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS. By providing rapid IDUA delivery to the brain, RGX-111 could potentially help prevent the progression of cognitive deficits that otherwise occurs in MPS I patients. RGX-111 has received orphan drug, rare pediatric disease, and Fast Track designations from the U.S. Food and Drug Administration.

“The structure of the agreement allows us to leverage our expertise in gene therapy manufacturing while also capturing milestones and a meaningful share of future product revenues,” said Curran Simpson, president and CEO of RegenxBio. “RGX-121 is poised to be the first gene therapy for MPS II with potential FDA approval as early as late 2025, and RGX-111 has demonstrated very promising results in phase 1/2 study. With Nippon Shinyaku’s expertise in rare disease and strong commercial capabilities, we look forward to working together to get both of these promising candidates across the finish line for patients.”