Homology Medicines is focused on advancing our genetic medicines platform as one-time treatments and potential cures for patients with rare diseases

Homology Medicines is focused on advancing our genetic medicines platform as one-time treatments and potential cures for patients with rare diseases

Release Details

Homology Medicines Announces Optimized, In Vivo Gene Therapy Candidate for the Treatment of Metachromatic Leukodystrophy

August 11, 2022

- 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, Mass., Aug. 11, 2022 (GLOBE NEWSWIRE) -- 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

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding our plans and timing for the release of additional preclinical and clinical data; our expectations surrounding the potential, safety, and efficacy of our product candidates; the potential of our gene therapy and gene editing platforms; our plans to engage in future collaborations and strategic partnerships; and our position as a leader in the development of genetic medicines. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; securities class action litigation; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property; risks associated with international operations, such as political and economic instability, including in light of the conflict between Russia and Ukraine; and significant costs incurred as a result of operating as a public company. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2022, and our other filings with the Securities and Exchange Commission (SEC) could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Company Contacts:
Theresa McNeely
Chief Communications Officer
and Patient Advocate 

Media Contact:
Cara Mayfield
Vice President, Patient Advocacy
and Corporate Communications 

Business Development Contact:
Kristi Sarno
Vice President, Business Development
and Corporate Strategy 

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Source: Homology Medicines, Inc.