2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-juMPStart: Phase 1, Open-Label, Dose-Escalation Safety and Efficacy Gene Therapy Study Evaluating HMI-203 in Adults with MPS II

Pdf Summary

The document is focused on the preclinical safety and efficacy of HMI-203, a gene therapy, in the treatment of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder. The disease is caused by mutations in the IDS gene, resulting in the loss of iduronate 2-sulfatase (I2S) enzyme activity and the accumulation of glycosaminoglycans (GAGs) in the body.<br /><br />The study found that HMI-203 demonstrated long-term I2S activity in liver tissue, with early and sustained secretion in serum. The active I2S was capable of cross-correction through the M6P pathway in the MPS II mouse model. The gene therapy significantly reduced GAG-HS levels in the cerebrospinal fluid and lysosomal burden in central nervous system tissues.<br /><br />HMI-203 was delivered as a one-time intravenous administration and showed widespread transduction and expression in peripheral organs and the central nervous system. The therapy resulted in sustained reduction of GAG-HS levels in tissues and urine, with durability observed up to 52 weeks post-administration.<br /><br />The safety of HMI-203 was evaluated in wild-type mice and no safety concerns were identified. A Phase 1 clinical trial, named juMPStart, has been initiated to evaluate the safety and efficacy of HMI-203 in adults with MPS II. The trial aims to assess the incidence and severity of treatment-emergent adverse events, as well as the mean percent change from baseline in urine GAG levels and I2S activity.<br /><br />The document also provides information on the disease manifestations of MPS II, the current standard of care using enzyme replacement therapy (ERT), and the potential of HMI-203 to address the unmet medical need for a treatment that targets both the peripheral and cognitive aspects of MPS II.<br /><br />The study concludes that the positive safety and efficacy results observed in the preclinical studies support the initiation of the clinical trial, and if successful, HMI-203 may provide a more effective treatment option for MPS II patients. The trial is currently ongoing, with recruitment taking place in the United States and Canada.

Asset Subtitle

Submitter Only - Michael Blum, MBA; Presenting Author - Gerry Shioshita, PharmD;

Meta Tag

Bone/Joint Abnormalities

Brain/Nervous System

Enzyme Replacement Therapy

Lysosomal Diseases

Presenting Author Gerry Shioshita, PharmD

Submitter Only Michael Blum, MBA

Keywords

gene therapy

HMI-203

Mucopolysaccharidosis type II

MPS II

lysosomal storage disorder

IDS gene

I2S enzyme

glycosaminoglycans

preclinical safety

efficacy