Under the terms of the agreement, Regenxbio will receive a $110 million upfront payment at closing and is eligible for up to $700 million more, including $40 million in potential development and regulatory milestones and $660 million in potential sales milestones. Regenxbio will also receive royalties on net sales.
“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 M. Simpson, President and CEO of Regenxbio in a press release.
“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 diseases and strong commercial capabilities, we look forward to working together to get both of these promising candidates across the finish line for patients.”
Also known as Hunter syndrome, MPS II is a rare genetic disorder belonging to the group of lysosomal storage disorders. As it is an X chromosome-linked disease, it affects mainly boys. Around 2,000 people worldwide have MPS II.
Affected persons have genetic variations in the IDS gene, which is needed for the production of the enzyme iduronate-2-sulfatase (I2S). I2S is normally found in cells’ lysosomes where it is responsible for breaking down complex sugars. People with MPS II, have a deficiency or altogether lack I2S, resulting in an excessive accumulation of complex sugars in the cells.
RGX-121 is an adeno-associated virus (AAV) therapeutic with the potential of being a one-time treatment for boys with MPS II. The protein expressed by RGX-121 has an identical structure to I2S. RGX-121 has previously received Orphan Drug Product, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the FDA, as well as the advanced therapy medicinal products classification from the EMA.
Unlike MPS II, MPS I – also known as Hurler syndrome – affects male and female children equally. MPS I occurs in approximately one in 100,000 births and is also a lysosomal storage disease. Mutations in the IDUA gene, result in a reduced production or complete lack of the enzyme alpha-L-iduronidase, which is also responsible for breaking down large sugar molecules.
While the symptoms of MPS II and I are similar, the severity of the symptoms is greater in persons with MPS I. Symptoms include macrocephaly, hydrocephalus, heart valve abnormalities, enlarged liver, spleen, tongue, and vocal cords, as well as corneal clouding, which can cause vision loss, and skeletal abnormalities. As MPS involves several organs and tissues, people with the most severe form experience intellectual decline, rapid disease progression, and loss of basic functional skills.
RGX-111 uses an AAV9 vector that delivers the IDUA gene to the central nervous system, where it could potentially stop the progression of cognitive decline that occurs in patients with MPS I. RGX-111 has also received Orphan Drug Product, Rare Pediatric Disease, and Fast Track designations from the FDA. In February 2023, positive interim data was reported from a Phase I/II trial.
“RGX-121 and RGX-111 represent one-time gene therapies that can potentially change the course of MPS disease, and we are very pleased to be partnering with Regenxbio, experts in gene therapy development and manufacturing,” said Toru Nakai, President and Representative Director of Nippon Shinyaku in a press release. “We are confident these therapies can bring tremendous value to those living with MPS II and I.”
