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Therapeutic Focus

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Therapeutic Focus

Our genetic medicines platform has the potential to treat and cure a wide range of rare diseases through gene therapy, gene editing or our GTx-mAb platform.

We are initially working to cure monogenic diseases, or diseases that are caused by a defect in a single gene. We are prioritizing diseases with significant unmet medical need and validated regulatory pathways to bring new treatments forward as rapidly as possible.

For each target, we are deploying a gene therapy, gene editing or GTx-mAb approach based on disease biology. In these approaches, we are using our proprietary human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to deliver the treatment to patients.

Gene editing involves the insertion of a corrected gene directly into the genome. With gene editing, a person’s DNA is permanently corrected. This approach can potentially be curative including in rapidly dividing cells (e.g., hematopoietic CD34+ cells and pediatric liver cells).

Gene therapy involves the transfer of corrected genes to specific cells in the body. With gene therapy, the genes do not integrate into the genome. This approach can be potentially curative in slow- or non-dividing cells (e.g., adult liver or central nervous system).

GTx-mAb is an extension of our gene therapy approach. It is designed to leverage our AAVHSCs to deliver one-time in vivo gene therapy using a construct with therapeutic cDNA for heavy chain and light chain antibody proteins that are delivered to the liver where they form fully functional, full-length Immunoglobulin G (IgG) antibodies and are secreted throughout the body.

Homology’s Genetic Medicines Pipeline

Phenylketonuria (PKU)

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 phenylalanine (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.

HMI-103 Gene Editing for Patients with PKU

Homology is conducting its Phase 1, open label, dose-escalation clinical trial (called the pheEDIT study) with the HMI-103 gene editing candidate for patients with PKU. HMI-103 is designed as a one-time in vivo product candidate incorporating nuclease-free gene editing for PKU. It harnesses the body's natural DNA repair process of homologous recombination to replace the disease-causing gene with a functional gene and liver-specific promoter to maximize long-term expression.

HMI-103 was granted Fast Track designation by the U.S. Food and Drug Administration.

Additional information about pheEDIT can be found at or

HMI-102 Gene Therapy for Adult Patients with PKU

Recently announced prioritization of PKU clinical programs to focus on the pheEDIT trial to move closer to the goal of offering solutions for both adults and pediatric patients with PKU. As a result, the Company paused enrollment in the pheNIX gene therapy trial evaluating HMI-102.

HMI-102 was granted Orphan Drug Designation and Fast Track Designation by the U.S. Food and Drug Administration and Orphan Drug Designation by the European Medicines Agency. 

Mucopolysaccharidosis Type II (MPS II), or Hunter syndrome 

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.

Homology is conducting a Phase 1 open-label dose-escalation clinical trial (called the juMPStart study). HMI-203 is a one-time gene therapy candidate for Hunter syndrome designed to use one of Homology’s AAVHSC vectors to deliver functional copies of the IDS gene to multiple organs where there are missing or mutated copies of the gene. 

HMI-203 was granted Orphan Drug Designation by the U.S. Food and Drug Administration. 

Additional information about juMPStart can be found at or

Metachromatic Leukodystrophy (MLD)

MLD is a rare lysosomal storage disorder primarily caused by a mutation 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 5-10 years after onset.

We are seeking a partner to advance HMI-204, an optimized, in vivo gene therapy candidate for MLD.

Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is a rare, acquired life-threatening blood disease caused by mutations in the PIGA gene that results in intravascular hemolysis, or red blood cell destruction, mediated by uncontrolled activation of the complement system. PNH results in thromboses, recurrent pain, severe anemia, kidney disease and impaired quality of life, among other outcomes.

We named a development candidate for PNH (HMI-104).