REGENXBIO Programs

RGX-501 for HoFH

RGX-501 is our product candidate for the treatment of homozygous familial hypercholesterolemia (HoFH), which is designed to use the AAV8 vector to deliver the human low-density lipoprotein receptor (LDLR) gene to liver cells.

HoFH is a monogenic disorder caused by abnormalities in the function or expression of the LDLR gene. HoFH patients have very low levels or are completely deficient of LDLR, resulting in very high total blood cholesterol levels. This leads to premature and aggressive plaque buildup, life threatening coronary artery disease (CAD) and aortic valve disease.

The current standard of care in HoFH focuses on early initiation of aggressive treatment due to severe clinical effects of elevated LDL-C. Available therapies do not provide a cure and their use is limited due to tolerability and drug availability.

We believe that the liver is the preferred target organ for gene therapy of HoFH since LDLRs produced in the liver contribute to greater than 90 percent of the capture and breakdown of LDL, making the liver by far the most important LDLR producing organ.

An Investigational New Drug (IND) application to support a Phase I/II clinical trial to evaluate the effect of RGX-501 in the treatment of HoFH is active. The IND was filed with the U.S. Food and Drug Administration (FDA) by the University of Pennsylvania, REGENXBIO’s development partner. RGX-501 has received orphan drug product designation from the FDA.

RGX-314 for wet AMD

RGX-314 is our product candidate for the treatment of wet age-related macular degeneration (wet AMD), which is designed to act by neutralizing the activity of vascular endothelial growth factor (VEGF) and modifying the pathway for formation of new leaky blood vessels and retinal fluid accumulation.

A subset of AMD patients have wet AMD, which is characterized by loss of vision due to the formation of new blood vessels into space between two layers of cells in the retina. Wet AMD is a leading cause of total and partial vision loss in the U.S., Europe and Japan.

Current therapies require repetitive intravitreal injections to maintain efficacy, and patients often experience vision loss with reduced frequency of treatment.

REGENXBIO plans to deliver RGX-314 subretinally using an AAV8 vector that is designed to encode a gene for a monoclonal antibody fragment which binds to VEGF and neutralizes VEGF activity. Ranibizumab is an FDA-approved monoclonal antibody fragment that binds to VEGF and has been extensively shown to be both efficacious and safe in wet-AMD patients when delivered repeatedly through intraocular injections.

An IND to support a Phase I clinical trial to evaluate the effect of RGX-314 in the treatment of wet AMD is active.

RGX-111 for MPS I

RGX-111 is our product candidate for the treatment of Mucopolysaccharidosis Type I (MPS I), which is designed to use the AAV9 vector to deliver the human α-l-iduronidase (IDUA) gene to the central nervous system (CNS). The severe form of MPS I is referred to as Hurler syndrome.

MPS I is a rare recessive genetic disease caused by deficiency of IDUA, an enzyme required for the breakdown of polysaccharides heparan sulfate and dermatan sulfate in the lysosomes of cells. Many patients develop symptoms related to glycosaminoglycan storage in the CNS, which can include excessive accumulation of fluid in the brain (hydrocephalus), spinal cord compression and cognitive impairment.

Current standard of care treatments cannot treat the CNS manifestations of MPS I and leave a significant unmet need for a method to safely achieve long-term IDUA reconstitution in the CNS.

Delivery of the enzyme that is deficient within cells in the CNS could provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. This strategy could also provide rapid IDUA delivery to the brain, potentially preventing the progression of cognitive deficits that otherwise occur in Hurler syndrome patients following bone marrow transplant.

We intend to file an IND in the first half of 2017 to support the initiation of an early phase, dose-escalation clinical trial of RGX-111-based gene delivery via CNS administration in subjects with MPS I. RGX-111 has received orphan drug product and rare pediatric disease designation from the FDA.

RGX-121 for MPS II

RGX-121 is our product candidate for the treatment of Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome, which is designed to use the AAV9 vector to deliver the human iduronate-2-sulfatase (IDS) gene to the central nervous system (CNS).

MPS II is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme IDS. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Developmental progression begins to plateau between three and five years of age, with regression reported to begin around six and a half years.

Specific treatment to address the neurological manifestations of MPS II and prevent or stabilize cognitive decline remains a significant unmet medical need.

Delivery of the gene encoding the enzyme that is deficient within cells in the CNS could provide a permanent source of secreted IDS beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. We believe this strategy could also provide rapid IDS delivery to the brain, potentially preventing the progression of cognitive deficits that otherwise occur in Hunter syndrome patients.

Preclinical studies have demonstrated the potential therapeutic benefit of AAV9-mediated IDS gene delivery to the CNS through the cerebrospinal fluid to address neurological manifestations of MPS II. We intend to file an IND in mid-2017 to support the initiation of an early phase, dose-escalation clinical trial of RGX-121-based gene delivery via CNS administration in subjects with MPS II. RGX-121 has received orphan drug product and rare pediatric disease designation from the FDA.

RGX-321 for XLRP

RGX-321 is currently in preclinical development for the treatment of X-linked retinitis pigmentosa (XLRP).

Retinitis pigmentosa (RP) is the most common inherited form of blindness, with an estimated 100,000 patients in the U.S. XLRP accounts for approximately 10 percent of RP, with 75 to 80 percent of XLRP cases due to mutations in the gene for retinitis pigmentosa GTPase regulator (RPGR). Mutations in RPGR are associated with a more severe form of the disease, causing early onset of disease and a relatively fast progression.

No therapies exist for RP beyond vitamin supplementation and sun protection, which may or may not slow disease progression.