Regenxbio advancing 2 gene therapies in pipeline for Batten

First patient dosed in Phase 1/2 trial of RGX-381 in children

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A first patient has been dosed in a Phase 1/2 clinical trial testing the gene therapy RGX-381 — one of two in Regenxbio‘s pipeline for late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease — as a treatment for the most common form of Batten disease, the company announced in a second-quarter corporate update.

The investigational therapy aims to treat eye problems associated with CLN2 disease. According to Regenxbio, the first data from the trial, involving children ages 1-12, are expected next year.

Additionally, early data from a single-patient study of another company gene therapy candidate — RGX-181, also for eye problems in CLN2 disease — will be shared at an upcoming annual meeting in Jerusalem, in Israel. That data, from the six-month follow-up of a child in Brazil treated with the one-time therapy, will be presented at the Society for the Study of Inborn Errors of Metabolism Annual Symposium meeting, to be held Aug. 29-Sept. 1.

“Overall, we’re making excellent progress … to bring leading, ground-breaking AAV therapeutics to patients in need,” said Kenneth T. Mills, president and CEO of Regenxbio.

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Early data support Regenxbio’s gene therapy program for CLN2 disease

2 treatments in Regenxbio pipeline focus on eye problems

Most cases of late infantile Batten disease are caused by mutations in the CLN2 gene, which provides instructions for producing an enzyme called tripeptidyl peptidase 1, or TPP1. This enzyme is located within lysosomes, which are a sort of cell recycling center. These organelles within cells are responsible for breaking down and reusing various kinds of molecules.

Genetic mutations in the CLN2 gene result in an impaired TPP1 enzyme and the accumulation of detrimental waste molecules within lysosomes.

This ultimately results in the death of cells, specifically nerve cells, triggering the onset of the disease’s neurological symptoms. Key among them are seizures and loss of vision.

The gene therapy RGX-181 is administered in a single injection into the brain to deliver a healthy copy of the TTP1 gene to cells of the central nervous system (CNS), comprised of the brain and spinal cord.

In preclinical studies with animal models of CLN2, a single injection of RGX-181 significantly eased the animals’ neurological symptoms and improved survival by boosting the levels of the TPP1 enzyme throughout the CNS.

RGX-181 has been granted rare pediatric disease and orphan drug status by the U.S. Food and Drug Administration. Both designations are meant to ease a potential medicine’s path to market with various incentives.

The other gene therapy for Batten in the Regenxbio pipeline, RGX-381, is designed to deliver the TPP1 gene directly to the retina, the layer of the eye containing light-sensitive cells. This therapy aims to stop retinal degeneration and vision loss by continuously supplying the TPP1 enzyme. No treatments are available to date for CLN2-related vision loss.

In preclinical studies using lab-grown CLN2 patient-derived retinal models, RGX-381 restored TPP1 production. It also prevented or decreased lysosomal waste buildup in a dose-dependent manner. In nonhuman primates, a single dose of RGX-381 led to sustained TPP1 levels in several eye fluids over three months without adverse effects.

The Phase 1/2 trial (NCT05791864) is testing two doses of RGX-381 in children with genetically and molecularly confirmed CLN2 disease.

It’s now recruiting up to 16 children, who must be receiving Brineura, among other eligibility critera. The study is underway at Great Ormond Street Hospital, in London.

In both gene therapies, the delivery of the TPP1 gene is achieved by using a viral carrier called an adeno-associated virus, which is modified in the lab to not cause disease.