Fortress Biotech Announces Publication of Preclinical Data on AAV-ATP7A Gene Therapy Combined with CUTX-101 (Copper Histidinate) for Menkes Disease in Molecular Therapy: Methods & Clinical Development
Fortress Biotech Announces Publication of Preclinical Data on AAV-ATP7A Gene Therapy Combined with CUTX-101 (Copper Histidinate)
for Menkes Disease in Molecular Therapy: Methods & Clinical Development
New York, NY, September 12, 2018 – Fortress Biotech, Inc. (NASDAQ: FBIO) (“Fortress”), a biopharmaceutical company dedicated to acquiring, developing and commercializing novel pharmaceutical and biotechnology products, today announced the publication of preclinical data on adenoassociated virus (AAV)-based gene therapy combined with subcutaneous CUTX-101 (Copper Histidinate) in a mouse model of Menkes disease, a fatal infantile disorder of human copper metabolism. In March 2017, Fortress’ subsidiary Cyprium Therapeutics, Inc. (“Cyprium”) licensed preclinical AAV-ATP7A gene therapy from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to develop in combination with CUTX-101. The data were published online and will be included in the September 21, 2018 edition of the journal Molecular Therapy: Methods & Clinical Development.
The preclinical study was conducted by the NICHD laboratory of Stephen G. Kaler, M.D., and evaluated low-, intermediate- and high-dose recombinant AAV serotype 9 (rAAV9)-ATP7A delivered to the cerebrospinal fluid (CSF) in combination with subcutaneous CUTX-101 in a mottledbrindled (mo-br) mouse model that closely mimics the biochemical and clinical phenotypes of Menkes disease. The rAAV9 construct carried the genetic instructions for a compact, reduced-size (rs) version of the Menkes copper transporter, ATP7A. Mutant mice that received high-dose CSFdirected rAAV9-rsATP7A in combination with CUTX-101 demonstrated improved long-term survival (53%) compared to mice that did not receive treatment (0%) or were administered either treatment by itself (0%, 0%). This synergistic treatment effect represents the most successful rescue to date of the mo-br mouse model. In addition, mutant mice treated with the high-dose CSF-directed rAAV9-rsATP7A in combination with CUTX-101 showed higher brain copper levels, normalized brain neurochemicals, improvement of brain mitochondrial abnormalities, and normal growth and neurobehavioral outcomes.
“We are highly encouraged by these preclinical data, which provide new insights on a potentially effective therapeutic approach for this difficult pediatric disease that currently has no FDA-approved treatment options,” said Lung S. Yam, M.D., Ph.D., President and Chief Executive Officer of Cyprium. “We have made excellent progress toward new drug approval of subcutaneous CUTX-101 for Menkes disease based on Dr. Kaler’s clinical trials and were granted FDA Fast Track Designation earlier this summer. We look forward to continuing to work with Dr. Kaler and NICHD to also advance the AAV-ATP7A gene therapy program toward the clinic and nominating a viral gene therapy candidate for drug development.”
The study “Cerebrospinal fluid-directed rAAV9-rsATP7A plus subcutaneous Copper Histidinate advance survival and outcomes in a Menkes disease mouse model” can be accessed online at: https://doi.org/10.1016/j.omtm.2018.07.002.
About Menkes Disease and Related Copper Metabolism Disorders
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 males, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment. Biochemically, Menkes patients have low levels of copper in their blood and brain, as well as abnormal levels of certain neurochemicals. Definitive diagnosis is typically made by sequencing the ATP7A gene. 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, and failure to thrive. Mortality is high in untreated Menkes disease, with many patients dying before the age of three. 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 CUTX-101 (Copper Histidinate)
CUTX-101 is in clinical development to treat patients with Menkes disease by replenishing Copper Histidinate, restoring copper homeostasis, and maintaining serum copper levels in the normal age appropriate range. CUTX-101 is a subcutaneous injectable formulation of Copper Histidinate manufactured under current good manufacturing practice (“cGMP”) that is intended to improve tolerability due to physiological pH and to bypass the oral absorption of copper, which is impaired in 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. A Phase 3 trial of CUTX-101 in patients with Menkes disease also led by Dr. Kaler has completed enrollment. A Cyprium-sponsored expanded access protocol for Menkes disease patients is ongoing.
About Cyprium Therapeutics
Cyprium 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 (“CRADA”) 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 addition, Cyprium and NICHD 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 Menkes patients, and to be used in combination with CUTX-101. CUTX-101 was granted FDA Fast Track and Rare Pediatric Disease Designations, and both CUTX-101 and AAV-ATP7A have received FDA Orphan Drug Designation previously. Cyprium was founded by Fortress Biotech, Inc. (Nasdaq: FBIO) and is based in New York City. For more information, visit www.cypriumtx.com.
About Fortress Biotech
Fortress Biotech, Inc. (“Fortress”) is an innovative biopharmaceutical company that was recently ranked number 10 in Deloitte’s 2019 Technology Fast 500™, an annual ranking of the fastest-growing North American companies in the technology, media, telecommunications, life sciences and energy tech sectors, based on percentage of fiscal year revenue growth over a three-year period. Fortress is focused on acquiring, developing and commercializing high-potential marketed pharmaceutical products and development-stage pharmaceutical product candidates. The company has five marketed prescription pharmaceutical products and over 25 programs in development at Fortress, at its majority-owned and majority-controlled partners and at partners 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 driven by a world-class business development team that is focused on leveraging its significant biopharmaceutical industry expertise 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 Alexion Pharmaceuticals, Inc., AstraZeneca, City of Hope, Fred Hutchinson Cancer Research Center, InvaGen Pharmaceuticals Inc. (a subsidiary of Cipla Limited), St. Jude Children’s Research Hospital and Nationwide Children’s Hospital. For more information, visit www.fortressbiotech.com.
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Jaclyn Jaffe and William Begien
Fortress Biotech, Inc.
Lung Yam, M.D., Ph.D.
Cyprium Therapeutics, Inc.
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