RGX-381 / REGENXBIO - LARVOL DELTA

First in-human intracisternal dosing of RGX-181 (adeno-associated virus 9 / human tripeptidyl peptidase 1) for a 5-year-old child with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2): 6 month follow-up (SSIEM 2023) - "Treatment involves biweekly intracerebroventricular enzyme replacement therapy (ERT) with cerliponase alfa via an indwelling port...RGX-181 is a recombinant adeno-associated virus serotype 9 vector (AAV9) containing a human CLN2 expression cassette (AAV9.CB7.hCLN2) designed to induce sustained secretion of TPP1 enzyme in the CNS...Prednisone, tacrolimus, and sirolimus were administered per the protocol’s immunosuppressive regimen...Discussion/Conclusion First-in-human administration of RGX-181 has been well tolerated to date. Observation and data collection are ongoing."

Clinical • First-in-human • P1 data • CNS Disorders • Epilepsy • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • TPP1

Progress in gene therapy for CLN2 Batten disease related retinopathy (ARVO 2025) - "The gene encodes TPP1, a lysosomal enzyme, that permits clearance of toxic lipofuschin particularly in neurons.The disease typically presents with loss of perifoveal ellipsoid at the age of 3-4 years progressing to loss of sub-foveal ellipsoid, and subsequent centripetal spread throughout the fundus; complete vision loss typically occurs by the age of 7-8 years.Intracerebroventricular infusions of the recombinent pro-enzyme rhTPP1 - cerliponase alfa - now mean that children are surviving the disease, but continue to go blind. Our previous work (ARVO poster 2023) has demonstrated intravitreal enzyme replacement slows the progress of decline which maybe dose dependent but studies of the frequency of injection and dose escalation are still required.At ARVO 2024 we presented interim data from the RGX-381 study of ocular CLN2 gene replacement therapy based on the initial 4 patients recruited up to day 180 follow-up...This programme has now transferred ownership to Tern..."

Gene therapy • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • TPP1

A First-in-Human, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of Gene Therapy with TTX-381 for the Ocular Manifestations Associated with Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: Tern Therapeutics, LLC | Active, not recruiting ➔ Recruiting | Trial completion date: Jul 2029 ➔ Jul 2030

Enrollment open • Trial completion date • CNS Disorders • Gene Therapies • TPP1

A First-in-Human Study in Pediatric Patients With Ocular CLN2 Disease (clinicaltrials.gov) - P1/2 | N=4 | Active, not recruiting | Sponsor: Tern Therapeutics, LLC | N=16 ➔ 4 | Trial completion date: Oct 2025 ➔ Jul 2029 | Trial primary completion date: May 2025 ➔ Jul 2026

Enrollment change • Gene therapy • Trial completion date • Trial primary completion date • CNS Disorders • Gene Therapies • Pediatrics • TPP1

Interim results for RGX-381: a first in human phase 1/2 clinical trial of AAV.CB7.hCLN2 gene therapy for CLN2 Batten disease-associated retinopathy (ARVO 2024) - "Cerliponase alfa (BioMarin), a recombinant proenzyme given via intracerebroventricular (ICV) infusion every 2 weeks, significantly ameliorates the neurological decline and children now survive; it does not affect the retinal dystrophy.RGX-381 (AAV9.CB7.hCLN2) is an investigational gene therapy comprised of a recombinant AAV9 vector that delivers a human CLN2 transgene with the aim of sustained secretion of TPP1 enzyme to prevent progressive photoreceptor degeneration. This first-in-human administration of RGX-381 has been well tolerated, with one resolved drug- and/or procedure-related AE as of Day 90. Efficacy data suggest a rapid restoration of TPP1 levels in the treated eye, and concomitant preservation of photoreceptors. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand."

Clinical • Gene therapy • P1/2 data • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • TPP1

A First-in-Human Study in Pediatric Patients With Ocular CLN2 Disease (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: REGENXBIO Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Gene Therapies • Pediatrics • TPP1

A First-in-Human Study in Pediatric Patients With Ocular CLN2 Disease (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: REGENXBIO Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • CNS Disorders • Gene Therapies • Pediatrics • TPP1

Treatment of a novel CLN2 patient-derived in vitro ocular model with RGX-381 gene therapy prevents or reverses lysosomal waste accumulation (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Gene therapy • Preclinical • Ophthalmology • TPP1

A First-in-Human Study in Pediatric Patients With Ocular CLN2 Disease (clinicaltrials.gov) - P1/2 | N=16 | Not yet recruiting | Sponsor: REGENXBIO Inc.

Gene therapy • New P1/2 trial • CNS Disorders • Gene Therapies • Pediatrics • TPP1