Cyprium Therapeutics, Inc. (“Cyprium”), a majority-owned subsidiary
of Fortress Biotech, Inc. (Nasdaq: FBIO) (“Fortress”), today
announced that the National Institute of Neurological Disorders and
Stroke (“NINDS”) of the National Institutes of Health (“NIH”) has
awarded a three-year grant totaling approximately $4.1 million to
the Research Institute at Nationwide Children’s Hospital and
Principal Investigator, Stephen G. Kaler, M.D., M.P.H., to fund
completion of preclinical studies, manufacturing and preparation of
an Investigational New Drug Application for a first-in-human
clinical trial to advance adeno-associated virus (“AAV”)-ATP7A gene
therapy, also known as AAV-ATP7A, for the treatment of Menkes
disease.
Often lethal if untreated, Menkes disease is an
X-linked recessive disorder of copper metabolism caused by
mutations in ATP7A, an evolutionarily conserved copper-transporting
ATPase. The minimum birth prevalence for Menkes disease is believed
to be 1 in 34,810 live male births, and potentially as high as 1 in
8,664 live male births, based on genome-driven ascertainment. In
2017, Cyprium entered into a worldwide, exclusive license agreement
with the Eunice Kennedy Shriver National Institute of Child Health
and Human Development (“NICHD”) to develop and commercialize
AAV-ATP7A gene therapy to deliver working copies of the copper
transporter defective in patients with Menkes disease, and to be
used in combination with CUTX-101 (Copper Histidinate), which is
being developed by Sentynl Therapeutics, Inc. (“Sentynl”).
AAV-ATP7A was previously granted Orphan Drug Designation by the
U.S. Food and Drug Administration (“FDA”).
“By combining CUTX-101 with working copies of
ATP7A delivered by AAV, we hope to enhance clinical outcomes in
Menkes disease, a fatal rare pediatric disease. This funding allows
us to further evaluate the preclinical safety, tolerability and
dosing of AAV9-codon-optimized, reduced-size ATP7A, which we
propose to administer in a first-in-human clinical trial for Menkes
disease. Advances in viral gene therapy and newborn screening make
it feasible to envision changing the natural history of this
difficult illness, in combination with CUTX-101, potentially the
first FDA-approved treatment for Menkes disease,” said Dr. Kaler, a
physician-scientist in the Center for Gene Therapy in the Abigail
Wexner Research Institute at Nationwide Children’s Hospital,
Principal Investigator of the preclinical and clinical studies, and
professor of Pediatrics and Genetics at The Ohio State University
College of Medicine.
Preclinical studies have demonstrated a
synergistic effect of AAV-ATP7A and CUTX-101 in a reliable mouse
model of Menkes disease. In early studies, cerebrospinal fluid
(“CSF”)-directed AAV gene therapy rescued 22-53% of mice with a
mutation in the human Menkes disease homolog (mottled-brindled)
when combined with CSF or subcutaneous copper. In addition, mutant
mice treated with CSF-directed AAV9- reduced-size ATP7A in
combination with CUTX-101 showed higher brain copper levels,
normalized brain neurochemicals, improvement of brain mitochondrial
abnormalities, and near-normal growth and neurobehavioral
outcomes.
More recently, based on successful intravenous
AAV9 gene therapy in mice and humans with spinal muscular atrophy
at the Center for Gene Therapy, Nationwide Children’s Hospital, the
Kaler Laboratory evaluated intravenous administration of
AAV9-codon-optimized, reduced-size ATP7A combined with subcutaneous
administration of CUTX-101 in Menkes disease mouse models. This
regimen led to 95% long-term rescue of mottled-brindled mutant mice
(n=19/20), using an AAV9 dose of 2.6 x 1013 vg/kg body weight, the
most successful long-term rescue of this mouse model to date.
Lindsay A. Rosenwald, M.D., Executive Chairman,
President and Chief Executive Officer of Fortress, stated, “We are
honored to have the NIH’s support, and Dr. Kaler’s and Nationwide
Children’s leadership, to progress the development of AAV-ATP7A
gene therapy, to help provide a more effective therapeutic option
to patients with Menkes disease. As we continue the research and
development of AAV-ATP7A in combination with CUTX-101, there is
great potential for this next generation approach to enhance the
treatment of Menkes disease, which currently has no FDA-approved
treatment. We look forward to continuing to advance AAV-ATP7A with
Dr. Kaler and supporting Sentynl as they finalize and complete the
NDA submission for CUTX-101.”
The content and research reported in this
release are solely the responsibility of the authors and do not
necessarily represent the official views of the NIH.
About AAV-ATP7A Gene
TherapyAAV-ATP7A is an adeno-associated virus (AAV)-based
gene therapy in preclinical development for the treatment of Menkes
Disease. AAV-ATP7A is being developed to deliver working copies of
the copper transporter that is defective in Menkes patients and to
be used in combination with CUTX-101 (Copper Histidinate).
AAV-ATP7A was developed in part under an Exclusive License
Agreement with the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD), and in conjunction with
the Research Institute at Nationwide Children’s Hospital and
Principal Investigator, Dr. Stephen G. Kaler.
About CUTX-101 (Copper
Histidinate)CUTX-101 is a subcutaneous injectable
formulation of Copper Histidinate in clinical development by
Sentynl Therapeutics to treat patients with Menkes Disease. In a
Phase 1/2 clinical trial conducted by Stephen G. Kaler, M.D.,
M.P.H., at the National Institutes of Health (“NIH”), early
treatment of patients with Menkes disease with CUTX-101 led to an
improvement in neurodevelopmental outcomes and survival. Cyprium
previously reported positive topline clinical efficacy results for
CUTX-101, demonstrating statistically significant improvement in
overall survival for Menkes disease subjects who received early
treatment (ET) with CUTX-101, compared to an untreated historical
control cohort, with a nearly 80% reduction in the risk of death.
Median overall survival (OS) was 177.1 months for CUTX-101 ET
cohort compared to 16.1 months for the untreated historical control
cohort. CUTX-101 has been granted FDA Breakthrough Therapy, Fast
Track, Rare Pediatric Disease and FDA Orphan Drug Designations.
Additionally, the European Medicines Agency granted Orphan Drug
Designation for CUTX-101. An expanded access protocol, administered
by Sentynl Therapeutics, for patients with Menkes disease is
ongoing at multiple U.S. medical centers. Sentynl acquired the
CUTX-101 program via asset purchase in December 2023 and will owe
Cyprium milestone and royalty payments in connection with the
development and commercialization of the product.
About Menkes Disease Menkes
disease is a rare X-linked recessive pediatric disease caused by
gene mutations of copper transporter ATP7A. The minimum birth
prevalence for Menkes disease is believed to be 1 in 34,810 live
male births, and potentially as high as 1 in 8,664 live male
births, based on recent genome-driven ascertainment (Kaler SG,
Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease
and ATP7A-related disorders based on the Genome Aggregation
Database (gnomAD). Molecular Genetics and Metabolism Reports 2020
June 5;24:100602). The condition is characterized by distinctive
clinical features, including sparse and depigmented hair (“kinky
hair”), connective tissue problems, and severe neurological
symptoms such as seizures, hypotonia, failure to thrive, and
neurodevelopmental delays. Mortality is high in untreated Menkes
disease, with many patients dying before the age of two years old.
Milder versions of ATP7A mutations are associated with other
conditions, including Occipital Horn Syndrome and ATP7A-related
Distal Motor Neuropathy. Currently, there is no FDA-approved
treatment for Menkes disease and its variants.
About Cyprium
TherapeuticsCyprium Therapeutics, Inc. (“Cyprium”) is
focused on the development of novel therapies for the treatment of
Menkes disease and related copper metabolism disorders. In March
2017, Cyprium entered into a Cooperative Research and Development
Agreement with the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (“NICHD”), part of the NIH, to
advance the clinical development of CUTX-101 (Copper Histidinate
injection) for the treatment of Menkes disease. In 2023, Cyprium
completed the transfer of its proprietary rights and assigned its
FDA documents pertaining to CUTX-101 Copper Histidinate product
candidate for the treatment of Menkes disease, to Sentynl
Therapeutics, Inc. Cyprium and NICHD also previously entered into a
worldwide, exclusive license agreement to develop and commercialize
adeno-associated virus (AAV)-based gene therapy, called AAV-ATP7A,
to deliver working copies of the copper transporter that is
defective in patients with Menkes disease, and to be used in
combination with CUTX-101; AAV-ATP7A is currently in pre-clinical
development and has been granted FDA Orphan Drug Designation.
Cyprium was founded by Fortress Biotech, Inc. (Nasdaq: FBIO) and is
based in Miami. For more information, visit www.cypriumtx.com.
About Fortress BiotechFortress
Biotech, Inc. (“Fortress”) is an innovative biopharmaceutical
company focused on efficiently acquiring, developing and
commercializing or monetizing promising therapeutic products and
product candidates. The company has eight marketed prescription
pharmaceutical products and over 25 programs in development at
Fortress, at its majority-owned and majority-controlled partners
and subsidiaries and at partners and subsidiaries it founded and in
which it holds significant minority ownership positions. Such
product candidates span six large-market areas, including oncology,
rare diseases and gene therapy, which allow it to create value for
shareholders. Fortress advances its diversified pipeline through a
streamlined operating structure that fosters efficient drug
development. The Fortress model is focused on leveraging its
significant biopharmaceutical industry expertise and network to
further expand the company’s portfolio of product opportunities.
Fortress has established partnerships with some of the world’s
leading academic research institutions and biopharmaceutical
companies to maximize each opportunity to its full potential,
including AstraZeneca, City of Hope, Fred Hutchinson Cancer Center,
St. Jude Children’s Research Hospital, Nationwide Children’s
Hospital and Sentynl. For more information, visit
www.fortressbiotech.com.
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press release may contain “forward-looking statements” within the
meaning of Section 27A of the Securities Act of 1933 and Section
21E of the Securities Exchange Act of 1934, as amended. As used
below and throughout this press release, the words “we”, “us” and
“our” may refer to Fortress individually or together with one or
more partner companies, as dictated by context. Such statements
include, but are not limited to, any statements relating to our
growth strategy and product development programs, ability to
generate shareholder value, ability of our products to receive
necessary approvals, including FDA approval, ability of our
products and therapies to help patients and any other statements
that are not historical facts. Forward-looking statements are based
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results, financial condition and stock price. Factors that could
cause actual results to differ materially from those currently
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financing and strategic agreements and relationships; our need for
substantial additional funds and uncertainty relating to
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product candidates successfully and on a timely basis; our ability
to attract, integrate and retain key personnel; the early stage of
products under development; the results of research and development
activities; uncertainties relating to preclinical and clinical
testing; risks relating to the timing of starting and completing
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Private Securities Litigation Reform Act of 1995. The information
contained herein is intended to be reviewed in its totality, and
any stipulations, conditions or provisos that apply to a given
piece of information in one part of this press release should be
read as applying mutatis mutandis to every other instance of such
information appearing herein.
Company Contacts:Jaclyn Jaffe and Nicole
McCloskeyCyprium Therapeutics, Inc.ir@cypriumtx.com
Fortress Biotech, Inc.(781) 652-4500ir@fortressbiotech.com
Media Relations Contact:Tony Plohoros6
Degrees(908) 591-2839tplohoros@6degreespr.com
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