REGENXBIO Looks to Take CLN2 Gene Therapy Treatment Into the Clinic

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Maryland-based REGENXBIO is expanding its gene therapy pipeline to include a new treatment for late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, one of the most common forms of Batten disease.

In an announcement this morning, REGENXBIO said the new product candidate, RGX-181, is based on the company’s proprietary NAV Technology Platform. CLN2 is a form of Batten disease caused by mutations in the tripeptidyl peptidase 1 (TPP1) gene. RGX-181 will use the company’s NAV AAV9 vector to deliver the targeted TPP1 gene to patients. The administered gene is sent to the central nervous system to induce sustained levels of TPP1, the company said in a statement. Preclinical animal models have shown a single treatment with RGX-181 resulted in “widespread distribution and sustained expression of the TPP1 enzyme in the CNS with significant improvements in neurobehavioral function and survival of the animals.”

REGENXBIO will submit an investigational new drug (IND) application for RGX-181 to the U.S. Food and Drug Administration (FDA) in 2019 in hopes of beginning global first-in-human clinical trial with clinical centers planned in the United States and Europe. REGENXBIO has two other CNS products, RGX-111 and RGX-121, in clinical trials for the treatment of Mucopolysaccharidosis Type I (MPS I) and Mucopolysaccharidosis Type II (MPS II) diseases, respectively. 

Olivier Danos, chief scientific officer of REGENXBIO, said the company’s NAV platform holds “tremendous promise for advancing this new product candidate in our neurodegenerative disease pipeline.” Danos noted that CLN2 is a fatal disease is rapidly progressing with no cure. Current treatment options for CLN2 include palliative care or enzyme replacement therapy, where recombinant TPP1 is administered into the lateral ventricles via a permanently implanted device on a biweekly basis, the company noted.

“Children with CLN2 disease experience an array of serious symptoms such as seizures, deterioration of language and motor skills, blindness, cognitive decline and premature death. The goal of our RGX-181 clinical program is to develop a single-dose treatment to halt progression of neurological decline and improve a broad range of these devastating symptoms experienced by children with CLN2 disease,” Danos said in a statement.

Kenneth Mills, president and chief executive officer of REGENXBIO, said because of the unmet need and with the potential for NAV gene therapy, the company believes CLN2 is a “natural addition” to its neurodegenerative disease pipeline.

“As we prepare to initiate dosing in our clinical trials of RGX-111 for MPS I and RGX-121 for MPS II, adding RGX-181 to our research pipeline furthers our commitment to finding potential cures for children affected by these extremely serious and life-threatening neurodegenerative conditions,” Mills said.

Earlier this year, Mills told BioSpace that in 2018 the company will have one of the most diverse pipelines of gene therapy. In addition to the gene therapies the company has in its own pipeline, REGENXBIO is also working with a number of partnerships. REGENXBIO has partnerships with Audentes, Shire and Ultragenyx. In June the company saw a $100 million payday due to its expanded relationship with AveXis, now a Novartis company, to develop treatments for spinal muscular atrophy (SMA). In January the two companies amended the 2014 license agreement for REGENXBIO’s gene therapy technology.