- Data Support PKU and Hunter Syndrome Clinical Trials and PNH Program -
BEDFORD, Mass., Oct. 21, 2021 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today four presentations of preclinical data spanning its clinical-stage gene therapy program for mucopolysaccharidosis type II (MPS II, or Hunter syndrome), clinical-stage gene editing program for phenylketonuria (PKU), GTx-mAb program for paroxysmal nocturnal hemoglobinuria (PNH) and assays to evaluate levels of pre-existing antibodies to the Company’s adeno-associated viral vectors (AAVHSCs) during the 2021 European Society for Gene & Cell Therapy Virtual Conference (ESGCT).
“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 Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. “We shared additional preclinical data from studies of our single-dose, I.V. gene therapy candidate for MPS II, and showcased gene editing data in the PKU and humanized murine models, including on- and off-target assessment confirming the precision of our nuclease-free in vivo gene editing. Encouraging data from our GTx-mAb platform showed a single dose resulted in sustained and robust expression of full-length antibodies from the liver consistent with anti-C5 therapeutics. Further, we presented details of the methods of our neutralizing antibody assays used in our clinical trial screening.”
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.
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 lead clinical program, HMI-102, is an investigational gene therapy for adults with phenylketonuria (PKU) and additional programs focus on lysosomal storage disorders including Hunter syndrome, 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 vectors (AAVHSCs) 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, internal manufacturing capabilities and broad intellectual property position the Company as a leader in genetic medicines. For more information, visit www.homologymedicines.com.
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 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; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs 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, 2021 and our other filings with the 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.
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