Homology Medicines Announces Optimized, In Vivo Gene Therapy Candidate for the Treatment of Metachromatic Leukodystrophy
- Category: DNA RNA and Cells
- Published on Friday, 12 August 2022 10:28
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- Candidate Showed Ability to Target Central Nervous System and Peripheral Organs
Following a Single I.V. Administration in MLD Model, a Key Differentiator from Available
Treatments and Product Candidates -
- Data Demonstrated Biodistribution to Brain Regions and Multiple Cell Types -
- Optimizations Included Significant Improvements in Expression, Productivity and Packaging -
- Homology Seeks Partner to Advance Development Candidate -
BEDFORD, MA, USA I August 11, 2022 I Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the details of HMI-204, its optimized, in vivo, one-time gene therapy product candidate for the treatment of metachromatic leukodystrophy (MLD). Following a single I.V. administration in the MLD murine model, the candidate crossed the blood-brain-barrier to the central nervous system (CNS) and reached key peripheral organs involved in MLD. As a rare and often fatal genetic disorder, efforts are underway in the U.S. and globally to implement prospective newborn screening for MLD. Homology is actively seeking a partner to advance this preclinical-stage candidate.
“Efforts to enhance our original MLD candidate led to our optimized candidate, which has a better therapeutic profile with respect to expression and packaging, while retaining its key differentiator of addressing the CNS and peripheral organ manifestations of the disease with a single I.V. administration,” said Albert Seymour, Ph.D., President and Chief Scientific Officer of Homology Medicines. “In addition to our understanding of MLD disease biology and our team’s prior experience in developing potential treatments for this disorder, we were able to apply our expertise in vector design and manufacturing to optimize our candidate. We believe that the preclinical data demonstrate its potential to make a meaningful difference for patients whose current treatment options are limited to ex vivo approaches that include difficult pre-conditioning regimens. We look forward to sharing data from this development candidate at future meetings.”
In the murine model of MLD, a single I.V. administration of the optimized gene therapy candidate, which uses one of Homology’s proprietary AAVHSC capsids, resulted in:
- Broad biodistribution to peripheral organs and the CNS;
- Expression of human ARSA (hARSA) levels in multiple brain regions and cell types, which were well-above the minimum levels of enzyme needed to correct the MLD disease phenotype*;
- hARSA activity levels in the brain that are predictive of functional improvements; and
- hARSA activity in the serum.
Additionally, optimizations led to significant improvements in vector yield and superior packaging for the candidate.
*Clin Chem. 2016 Jan; 62(1): 279–286.
About 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 sulfatides in cells. In MLD, sulfatides accumulate and destroy myelin-producing cells in the peripheral and central nervous systems 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.
About Homology Medicines, Inc.
Homology Medicines, Inc. is a clinical-stage genetic medicines company dedicated to transforming the lives of patients suffering from rare diseases by addressing the underlying cause of the disease. The Company’s clinical programs include HMI-102, an investigational gene therapy for adults with phenylketonuria (PKU); HMI-103, a gene editing candidate for PKU; and HMI-203, an investigational gene therapy for Hunter syndrome. Additional programs focus on metachromatic leukodystrophy (MLD), paroxysmal nocturnal hemoglobinuria (PNH) and other diseases. Homology’s proprietary platform is designed to utilize its family of 15 human hematopoietic stem cell-derived adeno-associated virus (AAVHSCs) vectors to precisely and efficiently deliver genetic medicines in vivo through a gene therapy or nuclease-free gene editing modality, as well as to deliver one-time gene therapy to produce antibodies throughout the body through the GTx-mAb platform. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a focus on rare diseases. Homology believes its initial clinical data and compelling preclinical data, scientific and product development expertise and broad intellectual property position the Company as a leader in genetic medicines. For more information, visit www.homologymedicines.com.
SOURCE: Homology Medicines