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
Complement-Related Disorders -
- 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,
“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
Also at the
“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
Highlights from Homology’s 2022 ASGCT Presentations
For the first time, Homology will present data on the optimization of HMI-103 and its MOA in the presentation, “Sustained Correction of a Murine Model of Phenylketonuria and Integration into the Genome Following a
- Dose-responsive phenylalanine (Phe) reduction and integration in Pahenu2 mice;
- On-target integration at the target human PAH locus with no evidence of off-target integration; and
- Supported clearance of the IND for the HMI-103 pheEDIT clinical trial.
Also related to Homology’s HMI-103 program, the Company presented, “Genome-Wide and Directed Integration Assays Identify and Quantify rAAV In
- The use of long-read sequencing is critical to ensure genomic DNA is analyzed and does not include episomal DNA; and
- When evaluating across the genome using long-read sequencing, the only site of DNA integration detected with HMI-103 was at the desired human PAH location.
Homology presented new data in the poster, “Sustained Expression of C5mAb in Presence of Murine and Human FcRn,” including:
- Sustained expression of C5 mAb observed in the presence of murine and human FcRn; and
- Utility of the GTx-mAb approach for paroxysmal nocturnal hemoglobinuria (PNH) and other complement-mediated disorders.
There were three presentations related to Homology’s family of 15 AAVHSCs, including the poster, “Naturally Occurring Variations at the 501 and 706 Residues on AAVHSC16 Contribute to Reduced Liver Tropism and Slower Serum Clearance.” This poster focused on the characterization and screening of AAVHSCs that led to identifying AAVHSC16’s substantially reduced liver tropism after I.V. administration, which could be meaningful for diseases focused on cardiac tissue, muscle or the CNS.
Related, in “The Structure of the 501 Residue on AAVHSC16 is Imperative to the Functional Binding to Cell Surface Glycans, Which is a Key Step in Successful Transduction,” the data showed:
- The 501 unique residue is key for the lack of galactose binding for AAVHSC16; and
- The amino acid at this location is key for the glycan binding and functional transduction of the vector.
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
In the presentation titled, “Capsid Selection Strategy for the Development of Gene Therapies Based on Structural and Functional Analyses of a Panel of AAVHSCs,” data supported Homology’s approach to leverage the most advantageous capsid for each specific disease the Company targets.
Homology Symposium and Webcast
Homology will be hosting a symposium today at
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 expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; the potential of our gene therapy and gene editing platforms; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. 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
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Source: Homology Medicines, Inc.