Homology Medicines Announces Presentations Across Gene Therapy and Gene Editing Programs, including GTx-mAb, at European Society of Gene & Cell Therapy Meeting
October 21 2021 - 07:00AM
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 modelHomology’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.
Forward-Looking Statements 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.
Company ContactsTheresa McNeelyChief
Communications Officer and Patient
Advocatetmcneely@homologymedicines.com781-301-7277
Media Contact:Cara Mayfield Vice President,
Patient Advocacy and Corporate Communications
cmayfield@homologymedicines.com 781-691-3510
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