Homology Medicines Announces First Data from IND-Enabling Studies with GTx-mAb Candidate HMI-104 for PNH, Which Demonstrated Sustained Expression of Functional C5mAb Levels, at the ASGCT Annual Meeting

2023-05-17

基因疗法临床研究

- New Preclinical Data Demonstrated Ability to Re-Dose with AAVHSCs Across Viral Clades, Potentially Expanding Possibilities of Genetic Medicine Programs in the Future -

- Presented Methods to Accelerate Identification of Genomic Sites that Result in Improved Homologous Recombination-Based Gene Editing Efficiency -

BEDFORD, MA, USA I May 16, 2023 I Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today six presentations supporting its gene editing, gene therapy and GTx-mAb programs at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting, including the first data from IND-enabling studies with HMI-104, the anti-C5 GTx-mAb development candidate for paroxysmal nocturnal hemoglobinuria (PNH). These preclinical data demonstrated that a one-time administration of HMI-104 resulted in sustained expression of C5 monoclonal antibody (C5mAb) levels, supporting the use of a one-time vectorized approach for PNH to enable continuous antibody production.

“Given the severity of PNH, which is a rare, acquired blood disorder, and the unmet need associated with chronically administered available therapies, HMI-104 could provide an important new one-time approach,” said Albert Seymour, Ph.D., President and Chief Executive Officer of Homology Medicines. “We are continuing to advance HMI-104 through IND-enabling studies as well as progress our GTx-mAb platform for ocular diseases, with potential for other indications with larger patient populations.”

Homology also presented for the first time non-clinical data that showed the potential to re-dose liver-targeted AAVs, including the Company’s AAVHSCs, across different clades of viruses without suppressing or modulating the immune system. Additionally, Homology highlighted methods to identify genomic sites with improved homologous-recombination (HR)-based gene editing integration, which could be used to enhance and streamline development of future product candidates.

Highlights from Homology’s ASGCT 2023 Presentations

HMI-104: GTx-mAb Development Candidate for PNH

Homology presented results from two dose range-finding studies in the poster, “Preclinical Studies with HMI-104, an AAVHSC Vectorized C5 Monoclonal Antibody, for the Treatment of PNH.” In both NOD SCID and humanized liver murine models, a single intravenous (I.V.) dose of HMI-104 resulted in:

AAVHSC Re-Dosing

In the poster, “Re-Dosing of Liver-Targeted AAV Within and Across Clades in Mice: Effects of Neutralizing Antibodies and Vector-Specific Factors,” Homology reported new data from preclinical studies delivering liver-specific gene expression vectors for PAH or FIX genes in the murine model of phenylketonuria (PKU), which showed:

AAVHSC-Mediated, Homologous Recombination-Based Gene Editing

In the poster, “The Method for Identification and Characterization of Sites of Homology Directed Strand Cross-Over Using rAAV Integration Vectors,” Homology shared methods to characterize regions in the genome that demonstrate higher levels of recombination, which can lead to higher efficiency HR-based gene editing.

AAVHSC Biodistribution

In the poster, “Ocular Biodistribution of AAVHSCs Across Species and Routes of Administration,” data showed that AAVHSCs target a diverse array of ocular cell types, which could allow for versatility in the development of genetic medicines. Specifically, AAVHSC transduction was shown following different routes of administration in the following cell types:

Immunosuppression Regimen Used in Ongoing Clinical Trials for PKU and Hunter Syndrome

In the poster, “Targeted Approach to Immunosuppression with AAV Gene Therapy: Nonclinical Support of Clinical Approaches,” Homology presented data from NHP studies with an AAVHSC expressing PAH, which showed the combination of a targeted T-cell inhibitor and steroid reduced neutralizing antibody formation and increased gene expression. These data support the immunosuppression regimen used in Homology’s ongoing gene editing and gene therapy clinical trials.

HMI-204: Gene Therapy Candidate for MLD

In the poster, “Gene Therapy Candidate for Metachromatic Leukodystrophy (MLD): Optimization of HMI-202 Leading to HMI-204 Nomination,” Homology highlighted preclinical data on its optimized HMI-204 gene therapy candidate for MLD. In addition to improvements in productivity and packaging, the data showed that a single I.V. infusion of HMI-204 in the murine MLD model resulted in:

These posters are available on the Publications and Presentations page on Homology’s website.

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-103, a gene editing candidate for phenylketonuria (PKU); HMI-203, an investigational gene therapy for Hunter syndrome; and HMI-102, an investigational gene therapy for adults with PKU. Additional programs focus on paroxysmal nocturnal hemoglobinuria (PNH), metachromatic leukodystrophy (MLD) 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 nuclease-free gene editing modality, gene therapy, or GTx-mAb, which is designed to produce antibodies throughout the body. Homology established an AAV manufacturing and innovation business in partnership with Oxford Biomedica, which was based on Homology’s internal process development and manufacturing 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