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Therapeutic Focus

Therapeutic Focus

Homology Medicines’ genetic medicines platform has the potential to treat and cure a wide range of genetic diseases through gene editing or gene therapy.

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 either a gene therapy or gene editing approach based on disease biology. In both 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).

Homology’s Genetic Medicines Pipeline

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-102 Gene Therapy for Adult Patients with PKU

Homology is conducting the Phase 2 dose expansion portion of a randomized, concurrently controlled, clinical trial (called the pheNIX study). HMI-102 is a gene therapy candidate designed to address the genetic cause of the disease by delivering functional copies of the PAH gene to adult patients using one of our proprietary AAVHSC vectors. 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. Additional information about the pheNIX trial can be found at or

HMI-103 Gene Editing for Pediatric Patients with PKU

We plan to initiate a Phase 1/2 dose-escalation trial in 2021 with a gene editing candidate for pediatric patients with PKU. Children’s livers are rapidly dividing so gene editing, in which a functional copy of the PAH gene is delivered using our AAVHSC vector and replaces the mutated copy in the genome, is the best approach for a potential cure for PKU in this patient population.

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 optimizing a gene therapy candidate (HMI-202) for the late infantile form of MLD.

Mucopolysaccharidosis Type II (MPS II), or 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.

We plan to initiate a Phase 1/2 dose-escalation trial in 2021 with a gene therapy development candidate (HMI-203) for mucopolysaccharidosis Type II (MPS II), or Hunter syndrome.