– Data Support PKU and Hunter Syndrome Clinical Trials and PNH Program –

BEDFORD, MA, USA I October 21, 2021 I 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.

SOURCE: Homology Medicines