Homology Medicines, Inc. announced enrollment and site status updates from the pheEDIT Phase 1 gene editing trial with HMI-103 for phenylketonuria (PKU) and the juMPStart Phase 1 gene therapy trial with HMI-203 for Hunter syndrome (MPS II). The first participant was recently dosed in the pheEDIT trial, with additional participants in screening. Homology expects to provide initial data from the trial mid-year 2023.

There are nine active clinical trial sites with more expected to be initiated throughout 2023. The juMPStart trial has five clinical sites in the U.S. and Canada with more expected to be initiated, and initial data is expected in the second half of 2023. Homology shared new preclinical data supporting the immunosuppression regimen incorporated in both the pheEDIT and juMPStart trials.

In non-human primates (NHPs), use of a prophylactic T-cell inhibitor combined with steroids reduced the neutralizing antibody (nAb) response to the AAVHSC vector and increased mRNA expression, compared to NHPs not receiving the regimen and to those receiving each agent alone. Homology plans to present these data at an upcoming scientific conference. Building on the unique mechanism of action of gene editing candidate HMI-103, Homology shared preclinical potency data.

HMI-103 is designed to use homologous recombination to integrate the PAH gene and a liver-specific promoter into the genome and to maximize PAH expression in all transduced liver cells. In the preclinical PKU model, the murine surrogate of HMI-103 was ten times more potent than non-integrating gene therapy vector HMI-102. In 2023, Homology plans to progress its pipeline of genetic medicines, including conducting IND-enabling studies of HMI-104, a one-time GTx-mAb development candidate for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

The Company is also focused on efforts to partner the optimized HMI-204 gene therapy candidate for metachromatic leukodystrophy (MLD), with near-term plans to present preclinical data from the program for the first time. The Company will continue to work with Oxford Biomedica Solutions, the AAV manufacturing and innovation business Homology established with Oxford Biomedica and that supplies Homology's programs. Oxford Biomedica Solutions recently announced that its platform has produced high-quality titers of E15 vg/L and achieved over 90% fully intact vector. Homology is conducting a Phase 1, open-label, dose-escalation clinical trial (called the pheEDIT study).

HMI-103 is a one-time, in vivo, nuclease-free gene editing candidate for PKU designed to harness the body's natural DNA repair process of homologous recombination to replace the disease-causing gene with a functional gene and liver-specific promoter and to maximize PAH expression in all transduced liver cells. PKU is a rare inborn error of metabolism caused by a mutation in the PAH gene. PKU results in a loss of function of the enzyme phenylalanine hydroxylase, which is responsible for the metabolism of Phe, an amino acid obtained exclusively from the diet.

If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease. According to the National PKU Alliance, PKU affects nearly 16,500 people in the U.S. with approximately 350 newborns diagnosed each year.

The worldwide prevalence of PKU is estimated to be 50,000 people. Homology is conducting a Phase 1, open-label, dose-escalation clinical trial (called the juMPStart study). HMI-203 is a one-time, in vivo gene therapy candidate for Hunter syndrome designed to use one of Homology's AAVHSC vectors to deliver functional copies of the iduronate-2-sulfatase (IDS) gene to multiple organs where there are missing or mutated copies of the gene.

Hunter syndrome is a rare, X-linked lysosomal storage disorder caused by mutations in the IDS gene, which is responsible for producing the I2S enzyme that breaks down large sugar molecules, or cellular waste, called glycosaminoglycans (GAGs). Severe Hunter syndrome results in toxic lysosomal accumulation of GAGs that causes progressive debilitation and decline in intellectual function. Hunter syndrome occurs in approximately 1 in 100,000 to 1 in 170,000 males, and the severe form leads to life expectancy of 10 to 20 years.