HMI-203 Leverages Ability to Cross Blood-Brain-Barrier Following I.V. Administration, and Preclinical Data Showed Improvements in Key Disease Biomarkers

Program Expands Homology’s CNS Portfolio

BEDFORD, MA, USA I October 22, 2020 I Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today a new in vivo gene therapy development program for the treatment of mucopolysaccharidosis type II (MPS II), or Hunter syndrome. Development candidate HMI-203 is a potential one-time AAVHSC treatment designed to deliver functional copies of the IDS gene to multiple target organs, including the peripheral and central nervous systems (PNS and CNS), following a single I.V. administration. Homology has initiated pivotal IND-enabling studies and scaled the new construct up to 500L by leveraging its plug and play commercial manufacturing platform to support a potential regulatory submission for HMI-203.

“We are pleased to unveil our third gene therapy program, which leverages the ability of our AAVHSC vectors to cross the blood-brain-barrier and blood-nerve-barrier, as well as reach other peripheral organs involved in MPS II. Our in vivo approach broadens our CNS portfolio and differentiates Homology’s HMI-203 from other programs in development for Hunter syndrome,” stated Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. “There remains a high unmet medical need for a treatment that addresses both the peripheral and cognitive effects of this fatal disorder. Our data in the MPS II murine model showed high levels of active I2S protein expression, systemic reductions in GAG accumulation, and improvements in phenotype. We look forward to our continued work to advance this potential treatment forward for the MPS II community.”

In preclinical studies, a single I.V. administration of HMI-203 resulted in systemic and CNS transduction and I2S expression, leading to a significant reduction in GAG levels in the brain, liver, heart, spleen, lung and kidney, compared to the vehicle-treated disease model. Prevention of phenotypic symptoms was also observed in the model. Secreted I2S collected from the in vivo preclinical model following HMI-203 administration was taken up by human cells in an additional in vitro experiment, which supports the potential of HMI-203 to result in cell cross-correction.

Homology plans to present data from the HMI-203 program at upcoming scientific conferences as it continues its IND-enabling studies.

About Mucopolysaccharidosis Type II (MPS II), Hunter Syndrome
MPS II, or Hunter syndrome, is a rare, X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (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.

About Homology Medicines, Inc.
Homology Medicines, Inc. is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homology’s proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicines in vivo either through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visit

SOURCE: Homology Medicines