Homology Medicines Presents Data from Investigational PKU and MLD Gene Therapy Programs that Demonstrate Preclinical Proof-of-Concept for Potential One-Time Therapies
For the first time, Homology presented preclinical data from the murine model and non-human primates that demonstrated that the HMI-202 gene therapy candidate crossed the blood-brain-barrier and the blood-nerve-barrier and increased levels of arylsulfatase a (ARSA) protein to therapeutic levels. In addition, preclinical data on gene therapy candidate HMI-102 showed that a single administration resulted in sustained Phe reduction and increased tyrosine and other important downstream biochemical metabolites in the PKU murine model.
“The MLD presentation is part of a growing foundation of HMI-202 data to support a future IND filing, and the PKU preclinical data supported the initiation of our Phase 1/2 trial, which is ongoing and expected to report initial data by the end of this year,” said
Highlights from the posters include:
HMI-202 gene therapy in development for MLD
- Single administration of HMI-202 resulted in therapeutic levels of human ARSA enzyme in the murine MLD model.
- HMI-202 modulated disease-relevant biomarkers through 48 weeks (end of study), including LAMP-1, myelin and lymphocyte protein transcript and sulfatides in central nervous system tissue in the murine model.
- Human ARSA protein levels in non-human primates confirmed crossing of the blood-brain-barrier and blood-nerve-barrier.
HMI-102 investigational gene therapy for PKU
- A single administration normalized blood Phe levels in the Pahenu2 murine model, which was sustained for 48 weeks, consistent with the lifespan of the model.
- There was a concomitant increase in downstream biochemical metabolites, including tyrosine, melanin and 5-HIAA, indicating that the metabolic pathway had been restored.
- Liver vector genomes were stable over time, and weight-based dosing from the murine model to the non-human primate model was confirmed.
- There were no adverse findings observed in a toxicology study in the murine model to the highest dose tested.
This poster received a Reviewers’ Choice Abstract award during the ASHG Meeting.
A 5-year retrospective study of individuals with PKU treated at two specialized U.S. clinics
- Phe concentrations in patients with classical PKU remained above the therapeutic threshold under current standard of care, which includes life-long dietary protein restriction.
- There is an unmet medical need for therapies to control blood Phe in patients with PKU.
For more information, please visit www.homologymedicines.com/publications.
About Phenylketonuria (PKU)
PKU is a rare, inherited inborn error of metabolism caused by mutations in the PAH gene. The current standard of care is a highly restrictive diet, but it is not always effective, and there are currently no treatments available that address the genetic defect in PKU. If left untreated, PKU can result in progressive and severe neurological impairment. PKU affects approximately 16,500 people in the U.S., and an estimated 350 newborns are diagnosed each year.
About Metachromatic Leukodystrophy (MLD)
MLD is a rare lysosomal storage disorder caused by mutations in the ARSA gene. ARSA is responsible for the creation of the arylsulfatase A (ARSA) protein, which is required for the breakdown of cellular components. In MLD, these cellular components accumulate and destroy myelin-producing cells in the peripheral and central nervous system leading to progressive and serious neurological deterioration. The late infantile form of the disorder is estimated to affect 1 in 40,000 people, and it is fatal within five to ten years after onset.
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Source: Homology Medicines, Inc.