Homology Medicines Announces Presentations Across Gene Therapy and Gene Editing Programs, including GTx-mAb, at European Society of Gene & Cell Therapy Meeting
- Data Support PKU and Hunter Syndrome Clinical Trials and PNH Program -
“This week’s data presentations showed the breadth of preclinical work undertaken to support our three clinical trials, and more recent development efforts to expand our gene therapy platform to deliver and generate antibodies in the liver,” said
Building on this week’s Phase 1 trial initiation for HMI-203 and supportive data presented at ASHG, Homology featured central nervous system (CNS) data in the presentation titled, “Blood-Brain-Barrier Crossing Leads to Long-Term Efficacy in the CNS of HMI-203: Gene Therapy Development Candidate for Mucopolysaccharidosis Type II (MPS II), or Hunter Syndrome,” which showed a single I.V. dose of HMI-203 in the MPS II murine model:
- Crossed the blood-brain-barrier and blood-cerebrospinal-fluid-barrier and led to widespread brain transduction;
- Led to dose-dependent transduction, expression and I2S activity, as well as dose- and time-dependent glycosaminoglycan-heparin sulfate (GAG-HS) and LAMP1 reductions in the brain;
- Achieved brain I2S activity levels comparable to wild type (WT) human brain tissue;
- Reduced CSF GAG-HS levels, which were correlative to brain GAG-HS levels; and
- Decreased Purkinje neuron (nerve cells in cerebellar cortex essential for coordination and motor control) cell loss and vacuolization in the brain.
Following Homology’s recent announcement of its pheEDIT clinical trial with nuclease-free gene editing candidate, HMI-103, data from IND-enabling studies were highlighted in, “HMI-103: An Investigational Gene Editing Vector for Phenylketonuria (PKU),” and showed that a single I.V. dose of HMI-103*resulted in:
- Sustained reduction of phenylalanine (Phe) in a PKU murine model on a normal chow diet, up to 41 weeks post-dose (end of study);
- No adverse findings in a GLP toxicology study and no evidence of germline transmission;
- mRNA levels in human hepatocytes from a humanized murine liver model were comparable to levels observed in the HMI-103-treated PKU model at similar doses and were also above the threshold level required to normalize blood Phe in the PKU model; and
- On-target integration was demonstrated at the human PAH locus with no evidence of off-target integration, as confirmed by next-generation sequencing.
*Murine version of HMI-103 was evaluated in the murine PKU model; human candidate HMI-103 was evaluated in the humanized murine liver model
Homology’s GTx-mAb platform was featured in the presentation titled, “Gene Therapy-mAb Platform Targets Complement Protein 5 Using AAVHSCs.” A single I.V. dose of an AAVHSC GTx-mAb showed:
- Expression of full-length antibodies from the liver consistent with anti-C5 therapeutic levels;
- Sustained and robust IgG expression in vivo in a humanized murine humanized liver model and a murine NOD-SCID model; and
- In vivo vector-expressed C5 mAb had potent functional activity as shown by an ex vivo hemolysis assay.
Building on previously published data on the low prevalence of pre-existing neutralizing antibodies (NAbs) to AAVHSCs, the presentation titled, “Neutralizing Antibody Prevalence Toward a Hematopoietic Stem Cell-Derived AAV and Immunoassays for Clinical Trial Enrollment,” showed:
- Correlation between the commonly used 50% transduction inhibition (50% TI) and a validated Three-Tier (3T) Nab assay in a population of North American commercial serum samples; and
- The 50% TI method demonstrated better sensitivity and the 3T Nab system demonstrated better specificity.
Both methods are used in the screening phase of Homology’s HMI-102 gene therapy pheNIX clinical trial to determine patient eligibility based on pre-existing Nabs.
For more information, please visit www.homologymedicines.com/publications.
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, including our GTx-mAb platform; our plans and timing for the release of additional preclinical and clinical data; our beliefs regarding our manufacturing capabilities; 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 capabilities of our manufacturing facility; 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; failure to obtain
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Source: Homology Medicines, Inc.