N-sulphoglucosamine sulphohydrolase (DNL126) / Denali Therap - LARVOL DELTA

Preliminary results from a Phase 1/2, first-in-human, open-label study of DNL126 in children with MPSIIIA (SSIEM 2026) - P1/2 | "Evaluation of additional cohorts at the recommended clinical dose is ongoing. Funder: Denali Therapeutics."

Clinical • First-in-human • P1/2 data • Hepatology • Lysosomal Storage Diseases

Phase 3 study design: evaluation of efficacy and safety of DNL126 in mucopolysaccharidosis IIIA (SSIEM 2026) - "DNL126 is a novel ERT designed to cross the BBB, with potential to be a disease-modifying treatment for MPS IIIA. This study will assess efficacy and safety of DNL126 across a broad age range of MPS IIIA participants."

Clinical • P3 data • Lysosomal Storage Diseases

Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) (clinicaltrials.gov) - P1/2 | N=20 | Active, not recruiting | Sponsor: Denali Therapeutics Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hunter Syndrome • Lysosomal Storage Diseases • Pediatrics

Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) (clinicaltrials.gov) - P1/2 | N=26 | Recruiting | Sponsor: Denali Therapeutics Inc. | N=20 ➔ 26

Enrollment change • Hunter Syndrome • Lysosomal Storage Diseases • Pediatrics

Denali Therapeutics Announces Initiation of BLA Filing for Accelerated Approval of Tividenofusp Alfa for the Treatment of Hunter Syndrome (MPS II) and Positive Ongoing Interactions with FDA on DNL126 Through START Program (GlobeNewswire) - "Denali Therapeutics...today announced that the company’s initiation of a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa for the treatment of Hunter syndrome (MPS II) has been received by the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA)....Denali expects to complete the BLA submission in the first half of May 2025 and continues to prepare for a potential commercial launch in the U.S. in late 2025 or early 2026."

FDA filing • Launch US • Hunter Syndrome

Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) (clinicaltrials.gov) - P1/2 | N=8 | Recruiting | Sponsor: Denali Therapeutics Inc. | N=16 ➔ 8

Enrollment change • Hunter Syndrome • Lysosomal Storage Diseases • Pediatrics

Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: Denali Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hunter Syndrome • Lysosomal Storage Diseases • Pediatrics

Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) (clinicaltrials.gov) - P1/2 | N=16 | Not yet recruiting | Sponsor: Denali Therapeutics Inc.

New P1/2 trial • Hunter Syndrome • Lysosomal Storage Diseases • Pediatrics

Systemic scAAV9.U1a.hSGSH delivery corrects brain biochemistry in mucopolysaccharidosis type IIIA at early and later stages of disease. (PubMed, Hum Gene Ther) - "In order to assess the efficacy of restoring the underlying biochemistry in the MPS IIIA brain, tail vein injections of self-complementary AAV9 human N-sulphoglucosamine sulphohydrolase (scAAV9.U1A.hSGSH) at 3 x 1013 vg/kg were administered to 6 and 16 week old MPS IIIA mice. These results demonstrate that the gene product is actively clearing primary heparan sulphate and secondary ganglioside accumulation in MPS IIIA mice but in older mice, neurocognitive impairments remain. This is likely due to secondary downstream consequences of heparan sulphate affecting neurological functions that are not reversible upon substrate clearance."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Gene Therapies • Hunter Syndrome

Bioinformatics classification of mutations in patients with Mucopolysaccharidosis IIIA. (PubMed, Metab Brain Dis) - "The sulfamidase is produced by the N-sulphoglucosamine sulphohydrolase (SGSH) gene...The present results reveal the effects of three mutations on the enzymatic activity of sulfamidase, providing a molecular explanation for the cause of the disease. Thus, this study allows for a better understanding of the effect of SGSH mutations through the use of various computational approaches in terms of both structure and functions and provides a platform for the development of therapeutic drugs and potential disease treatments."

Clinical • Journal • CNS Disorders • Gene Therapies • Genetic Disorders • Mental Retardation • Oncology