Homology Medicines Presents Details of Optimized HMI-103 Nuclease-Free Gene Editing Candidate Featuring Integrated Liver-Specific Promoter to Maximize Long-Term Expression
- Additional Data at ASGCT Annual Meeting Demonstrate Precision of HR-Based Approach with Genome-Wide Integration Assays Confirming On-Target Editing and No Off-Target Events -
- New Data from GTx-mAb Platform Support Potential for Targeting Many
- Further Characterization of Homology’s Naturally Derived AAVHSC Capsids Highlight Their Broad Biodistribution and a Novel Discovery Revealed One Capsid with Low Tropism to the Liver, a Key Functional Benefit for Selecting New Disease Indications -
- Homology Symposium to be Held Today, May 18, at 7:30 a.m. ET -
BEDFORD, Mass., May 18, 2022 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, unveiled today the mechanism of action (MOA) and optimization of HMI-103, the nuclease-free gene editing candidate currently in a Phase 1 trial for phenylketonuria (PKU). HMI-103 utilizes the body’s natural DNA repair process of homologous recombination (HR) to insert a functional copy of the PAH gene into a specific region of the genome. It is designed to provide a permanent DNA correction for PKU by replacing at least one disease-causing allele with a normal gene sequence in edited cells. HMI-103 was optimized to integrate the PAH gene and a liver-specific promoter into the genome and to maximize enzyme expression in all transduced cells.
“Our dedication to providing new solutions for patients living with PKU led us to develop an AAV-based nuclease-free gene editing vector with a new MOA,” said Albert Seymour, Ph.D., President and Chief Scientific Officer of Homology Medicines. “We believe an innovative approach that combines a permanent correction in the genome while providing expression in all cells that are transduced will be an important advance in the field of gene editing. Preclinical data from our optimized HMI-103 in PKU showed Phe normalization and durability of expression, which is the ultimate goal for treating younger patients whose livers are still growing and dividing.”
Also at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, Homology presented data from its long-read, genome-wide integration assays, which confirmed the precision of HR-based integration of HMI-103, including no off-target editing in human hepatocytes in a humanized murine liver model. In addition, Homology shared new data from its GTx-mAb platform showing sustained antibody levels in murine and humanized models. The characterization of AAVHSC16 that has low tropism to the liver was also presented, which is a novel finding that provides opportunities to target additional diseases with a potentially lower immunogenicity profile.
“AAVs are ideal gene delivery vehicles for many disorders; however, the high liver tropism that many exhibit can limit their use in certain diseases,” continued Dr. Seymour. “Our family of 15 AAVHSC capsids have unique properties, and we have been focused on characterizing and leveraging them across our platform. We believe the new discovery that AAVHSC16 was able to target key tissues such as the CNS, muscle and cardiac tissue following a single I.V. administration, while having a very low affinity for the liver, may enable us to expand into new disease areas.”
Highlights from Homology’s 2022 ASGCT Presentations
In Vivo, Nuclease-Free Gene Editing Candidate HMI-103
Also related to Homology’s HMI-103 program, the Company presented, “Genome-Wide and Directed Integration Assays Identify and Quantify rAAV In Vivo/em> Gene Editing Sites in Mice with Humanized Livers,” which showed:
In an oral session, Homology presented, “rAAV Vector Breakpoints Determined Using Single-Molecule, Modified Base Sequencing,” that demonstrated the ability to identify, resolve and redesign rAAV vectors with the assistance of the long-read sequencing technology.
AAVHSC Capsid Selection Strategy
Homology Symposium and Webcast
About Homology Medicines, Inc.