Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines
company, announced today the pheEDIT Phase 1 clinical trial for
HMI-103, a one-time, in vivo product candidate that utilizes a gene
editing approach for phenylketonuria (PKU), based on the
Investigational New Drug Application (IND) clearance from the U.S.
Food and Drug Administration (FDA). HMI-103 will be the world’s
first gene editing candidate for PKU to enter clinical trials from
Homology’s dual gene therapy and gene editing technology platform,
and with the launch of pheEDIT Homology moves closer to its goal of
offering solutions for both adults and pediatric patients with PKU.
“Today’s milestone is the culmination of our team’s tireless
work to translate our gene editing technology from an academic
discovery into a clinical program for people with PKU,” said Albert
Seymour, Ph.D., Chief Scientific Officer of Homology Medicines.
“Our positive preclinical data in the PKU model demonstrated
phenotypic correction, and the precision of HMI-103 genome
integration was confirmed in a humanized liver model, which showed
no evidence of off-target mutations or unwanted on-target changes
to the genome. These nonclinical data give us great confidence in
initiating our Phase 1 pheEDIT trial, and we look forward to
continuing to work with the PKU community on our clinical
programs.”
The HMI-103 pheEDIT trial is expected to enroll up to nine
patients ages 18-55 years old who have been diagnosed with PKU due
to PAH deficiency. Once positive safety and efficacy results are
established in the adult population, Homology plans to enroll
younger patients in clinical trials. The Phase 1 dose-escalation
trial is designed to evaluate three doses of HMI-103 to determine
the recommended dose(s) for a future trial. In addition to safety
endpoints, the trial will measure serum phenylalanine (Phe)
changes.
HMI-103 is designed as a one-time administration to maximize the
expression of functional phenylalanine hydroxylase (PAH) in liver
cells and thus restore the natural biochemical pathway that
metabolizes Phe. The product candidate was developed to
specifically integrate a functional PAH gene into the genome using
the natural DNA repair process of homologous recombination. In
addition to expression, the integration is designed to
correct the cell by inactivating at least one of the mutated genes
and enable that correction to persist through cell
division.
Homology expects that the first patient in the pheEDIT clinical
trial will be dosed following requisite Institutional Biosafety
Committee and Institutional Review Board approvals at the clinical
sites. The trial will include an 82-day screening/run-in period
prior to HMI-103 administration.
Homology also announced today an update from its ongoing Phase 2
pheNIX clinical trial evaluating HMI-102 gene therapy in adults
with PKU. As of September 30, 2021, both doses in the trial have
been generally well-tolerated and have shown evidence of biological
activity, including clinically meaningful reductions in Phe levels,
increases in Tyr and reductions in the Phe-to-Tyr ratio. Several
new clinical trials sites have also recently been added to pheNIX
for a total of 13 with more sites expected shortly. Despite
increased interest, enrollment is slower than anticipated due in
part to COVID-19 resurgence, and the Company anticipates providing
a more detailed pheNIX update in mid-2022 when it expects to have a
larger dataset.
“We continue to be encouraged by the data from our pheNIX trial
and to hasten enrollment, we have expanded our Medical Affairs,
Clinical Development and Operations teams to support not only
pheNIX, but now pheEDIT and our Hunter syndrome gene therapy trial
expected this year,” said Arthur Tzianabos, Ph.D., President and
Chief Executive Officer of Homology Medicines. “The flexibility of
our technology platform enables us to develop gene therapy and gene
editing product candidates as potential one-time treatments, and
news today of our first trial that incorporates gene editing for
PKU demonstrates our ability to employ both approaches in an effort
to support the PKU community.”
PKU is caused by mutations in the PAH gene, which is responsible
for producing the enzyme that metabolizes Phe from dietary protein.
As a result, Phe accumulates to toxic levels in the blood and brain
and does not convert to melanin or the amino acid tyrosine (Tyr), a
precursor to neurotransmitters. Homology’s approach to PKU with
gene therapy and gene editing candidates is designed to treat both
the adult and pediatric communities with one-time treatments that
address the genetic cause of PKU. Since gene therapy does not
integrate into the genome, it can be used in cells that are not
rapidly dividing, such as an adult liver. Gene editing is designed
to make a permanent correction in cells, including those that are
rapidly dividing, such as a child’s liver.
About HMI-102 Gene Therapy and HMI-103 Gene Editing
Product Candidates HMI-102 is an investigational gene
therapy in clinical development for the treatment of
phenylketonuria (PKU) in adults. HMI-102 is designed to encode the
PAH gene, which is mutated in people with PKU, and delivered via
the liver-tropic AAVHSC15 vector. Homology has received Fast Track
Designation and orphan drug designation for HMI-102 from the U.S.
Food and Drug Administration (FDA), and orphan drug designation
from the European Medicines Agency (EMA).
HMI-103 is an investigational, nuclease-free gene editing
product candidate ultimately designed to treat pediatric patients
with PKU, whose livers are rapidly dividing, following initial
clinical trials in adults. HMI-103 also uses AAVHSC15 and is
designed to encode the PAH gene flanked by homology arms, or long
stretches of DNA, to target the PAH region of the genome. Using the
body’s natural DNA repair process of homologous recombination, the
PAH gene integrates into the genome. HMI-103 is designed to express
phenylalanine hydroxylase (PAH) and integrate into the PAH gene to
restore the natural biochemical pathway that metabolizes
phenylalanine (Phe).
About Phenylketonuria (PKU)PKU is a rare inborn
error of metabolism caused by a mutation in the PAH gene. PKU
results in a loss of function of the enzyme phenylalanine
hydroxylase (PAH), which is responsible for the metabolism of
phenylalanine (Phe), an amino acid obtained exclusively from the
diet. If left untreated, toxic levels of Phe can accumulate in the
blood and result in progressive and severe neurological impairment.
Currently, there are no treatment options for PKU that target the
underlying genetic cause of the disease. According to the National
PKU Alliance, PKU affects nearly 16,500 people in the U.S. with
approximately 350 newborns diagnosed each year. The worldwide
prevalence of PKU is estimated to be 50,000 people.
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 targeting 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 gene editing in PKU, 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 and
believes that its data, 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 expectations surrounding clinical trial enrollment;
our plans and timing for the commencement of and the release of
data from clinical trials; our beliefs regarding our manufacturing
capabilities; and our position as a leader in the development of
genetic medicines. 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; difficulties or delays enrolling patients in clinical
trials; 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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