FBIO - Fortress Biotech and Cyprium Therapeutics Announce $4.1 Million Grant from NINDS to Further Development of AAV-ATP7A Gene Therapy for Menkes Disease | Benzinga
Encouraging preclinical studies demonstrate potential to combine AAV-ATP7A gene therapy with CUTX-101, which could be the first FDA-approved treatment for Menkes disease
Cyprium Therapeutics, a majority-owned subsidiary of Fortress Biotech, is developing AAV-ATP7A gene therapy to be used in conjunction with CUTX-101 for the treatment of Menkes disease
MIAMI, March 04, 2024 (GLOBE NEWSWIRE) -- 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 ...