REGENXBIO and Nippon Shinyaku Announce $810M Exclusive Collaboration on Two AAV Gene Therapy Programs for MPS I and MPS II

On January 14 (local time), REGENXBIO and Nippon Shinyaku Co., Ltd. announced an exclusive collaboration in the field of AAV gene therapy to develop and commercialize RGX-121, a gene therapy for mucopolysaccharidosis type II (MPS II, also known as Hunter syndrome), and RGX-111, a gene therapy for mucopolysaccharidosis type I (MPS I, also known as Hurler syndrome).

Under the terms of the agreement, REGENXBIO will receive an upfront payment of $110 million. Upon achievement of certain milestones, REGENXBIO will also be eligible for additional payments of up to $700 million, comprising $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 (collectively, the “Licensed Territory”). (Totaling $810 million, approximately RMB 5.938 billion)

Nippon Shinyaku will commercialize these two products within the licensed territory (the United States and Asia), while REGENXBIO retains the rights to develop and commercialize them in countries outside the licensed territory. Future clinical development of RGX-121 and RGX-111 will be led by REGENXBIO, which also retains all rights to any Priority Review Voucher (PRV) that may be awarded for RGX-121, as well as 100% of any sales-related revenues received post-approval. RGX-121 is expected to receive accelerated approval in 2025, with the Biologics License Application (BLA) submission currently underway.

REGENXBIO is a gene therapy company founded in 2008, focused on developing gene therapy candidates for the treatment of retinal, metabolic, and neurodegenerative diseases. All of the company’s candidates are derived from its proprietary AAV viral vector platform (the NAV Technology Platform), including the two pipeline assets involved in this collaboration.

NAV vectors are modified AAVs capable of overcoming issues such as the immunogenicity associated with early-generation AAV vectors (AAV1–AAV6). Furthermore, pathogenic genes have been removed from NAV vectors themselves, ensuring they do not cause disease in humans. The NAV technology platform is a proprietary AAV gene delivery platform comprising exclusive rights to over 100 novel AAV vectors, including AAV7, AAV8, AAV9, and AAVrh10. These AAV vectors can target different parts of the body for diverse therapeutic applications; for instance, gene therapies delivered to the liver hold potential for treating metabolic disorders such as hemophilia, while those delivered to the central nervous system (brain and spinal cord) primarily target diseases affecting the brain and cognition. The key advantages of the NAV technology platform include low immunogenicity, ease of manufacturing, high and sustained gene expression, and diverse tissue specificity.

The other partner, Nippon Shinyaku Co., Ltd., is a Japanese company established in 1919 that manufactures pharmaceuticals and health supplements. In terms of pharmaceutical R&D, Nippon Shinyaku has established a presence in multiple therapeutic areas, including the nervous system, respiratory system, cardiovascular system, metabolic system, urinary system, digestive system, and oncology. On the product front, the company produces drugs for the urinary, nervous, respiratory, and circulatory systems, as well as analgesics and anti-inflammatory agents.

In addition to earning the favor of Nippon Shinyaku Co., Ltd., a century-old pharmaceutical company, REGENXBIO has also collaborated with multinational corporation (MNC) giants such as Novartis, AbbVie, Eli Lilly, Takeda, and Astellas, leveraging its proprietary NAV Technology Platform.

Among them, the most widely recognized product is Zolgensma, a gene therapy for spinal muscular atrophy (SMA) developed in collaboration with Novartis.(The rare disease drug that was subject to the National Healthcare Security Administration’s “soul-searching price negotiation” is also an SMA medication, namely Biogen’s nusinersen sodium injection, with its price reduced from RMB 700,000 per dose to RMB 33,000 per dose).

Regenxbio provided the most pivotal technology in the development of Zolgensma. Zolgensma utilizes AAV9 from Regenxbio’s NAV Technology Platform as its vector. The viral capsid binds to galactose on the cell surface, enabling AAV9 to cross the blood-brain barrier and deliver the SMN gene-containing AAV9 vector to motor neurons in the central nervous system.

As the world’s first gene therapy for spinal muscular atrophy, Zolgensma was launched in the United States in 2019. With a per-patient treatment cost of nearly $2.1 million (equivalent to RMB 15 million), it has been dubbed the “most expensive drug in history.” However, as a gene therapy, Zolgensma requires only a single dose to achieve therapeutic effects, thereby securing a substantial market presence abroad; its sales reached $1.214 billion in 2023.

One of the pipeline assets in this transaction, RGX-121, is also poised to become a landmark blockbuster therapy. RGX-121 is a candidate product for the treatment of MPS II, designed to deliver the human iduronate-2-sulfatase (IDS) gene to the central nervous system (CNS) using an AAV9 vector.

Mucopolysaccharidosis (MPS) is a rare lysosomal storage disorder caused by genetic mutations that lead to a deficiency in key enzymes, thereby impairing the degradation of glycosaminoglycans and resulting in their accumulation within the body. This accumulation damages multiple organ systems, including the skeletal system, heart, liver, eyes, and nervous system. The disease involves dysfunction across multiple systems, with an incidence rate of approximately 1 in 100,000. Despite its relatively low incidence, MPS is a severe, potentially life-threatening genetic disorder due to the extensive impact of lysosomal storage diseases and their irreversible pathological processes, necessitating continuous metabolic management and other supportive therapies.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S), leading to the accumulation of glycosaminoglycans (GAGs) and ultimately resulting in cellular, tissue, and organ dysfunction. It is estimated that MPS II affects 1 in 100,000 to 170,000 newborns. Children with severe MPS II may achieve early developmental milestones, but developmental delays become evident between 18 and 24 months of age. Targeted therapies for the neurological manifestations of MPS II remain a significant unmet medical need.

Key biomarkers of iduronate-2-sulfatase (I2S) enzyme activity in patients with mucopolysaccharidosis type II (MPS II) include its substrate, heparan sulfate (HS) D2S6, which has been shown to correlate with the neurocognitive manifestations of the disease. RGX-121 is a potentially one-time adeno-associated virus (AAV) gene therapy that expresses a protein structurally identical to normal I2S. By delivering the IDS gene into cells of the central nervous system (CNS), RGX-121 provides a permanent source of secreted I2S beyond the blood-brain barrier, thereby enabling long-term cross-correction of cells throughout the CNS.

Previously, data from the Phase 1/2/3 trial of RGX-121 for treating MPS II patients under 19 years of age were positive, with reports indicating that patients have sustained benefits from RGX-121 for up to three years. Curran M. Simpson, President and Chief Executive Officer of REGENXBIO, also stated, “RGX-121 is expected to receive FDA approval by the end of 2025, becoming the first gene therapy for MPS II. Another therapy, RGX-111, has also shown very promising results in its Phase 1/2 study.”

References:

1. "The Birth of the Sky-High-Priced Drug Zolgensma from the Perspective of Patent Licensing"

2. “Successful Completion of Pre-BLA Meeting: FDA Supports Accelerated Approval of REGENXBIO’s Gene Therapy for Mucopolysaccharidosis”

3. “ReGenXBio: A Rising Star in the Field of AAV Gene Therapy”