The Children's Hospital Corp.

Results show potential for gene therapy to improve long-term cardiac outcomes PHILADELPHIA, Nov. 18, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) announced encouraging results from the first ever gene therapy trial for Danon disease (DD), a rare, X-linked heart condition caused by a single gene mutation. The phase 1 trial was a collaboration between CHOP and the University of California, San Diego Medical Center, the University of Colorado, Anschutz Medical Center, Boston Children's Hospital and Rocket Pharmaceuticals. The data on the results of the RP-A501 Phase 1 trial, presented at a late breaking session today at the American Heart Association Scientific Sessions 2024 in Chicago, were also published in the New England Journal of Medicine. Continue Reading Joseph Rossano, MD, MS, FAAP, FACC, Chief of the Division of Cardiology at CHOP and one of the principal investigators in the RP-A501 Phase 1 trial. Danon disease (DD) is a rare genetic disorder that affects several tissues and organ systems in the body. It is a type of lysosomal storage disease (LSD), which occurs when the body does not have the necessary protein cells to properly metabolize and recycle waste. When this type of protein is missing, there is an unhealthy buildup of material in cells that leads to DD. Common symptoms include thickening or weakening of the heart muscle (also known as severe hypertrophic cardiomyopathy), weakening of arm and leg muscles, poor muscle tone (also known as skeletal muscular myopathy), cognitive delays and vision impairment. As a leader in innovative cell and gene therapies, pediatric cardiac treatment and robust research, participating in these groundbreaking collaborations was a natural progression for CHOP. "There's an urgent need for new therapies for young patients with Danon disease," said Joseph Rossano, MD, MS, FAAP, FACC, Chief of the Division of Cardiology at CHOP and one of the principal investigators in the RP-A501 Phase 1 trial. "Our results suggest gene therapy has the potential to improve long-term cardiac outcomes in this highly aggressive and fatal genetic disorder." In this study, sponsored by Rocket Pharmaceuticals, Inc., seven male patients ages 11-21 received a single infusion of RP-A501. RP-A501 is an experimental adeno-associated virus (AAV)-based gene therapy, which replaces the missing or nonworking LAMP-2 gene with a normal LAMP-2B gene. Patients also received immunosuppressants for several months. Of the study site participants, CHOP administered gene therapy solely to pediatric patients, while the University of California, San Diego treated both pediatric and adult patients. LAMP-2 is the gene responsible for telling the body how to produce proteins that metabolize and recycle waste. Mutations of LAMP-2 can cause DD, which is carried on the X chromosome. Researchers focused on young male patients because boys typically have a more severe version of the disease due to having one X chromosome compared with girls who have two, which can dilute the effect of a single mutated gene. Overall, the researchers found that RP-A501 can arrest and reverse underlying genetic, molecular, and cellular causes of DD. Over 24-54 months of follow-up, the patients' symptoms significantly improved, suggesting that the therapy has the potential to help patients achieve long-term positive outcomes. In CHOP's cohort, the researchers observed that children taking immunosuppressants experienced less muscle weakness in three to six-months. Based on the positive results, a global Phase 2 registrational-enabling study assessing the safety and efficacy in male patients with DD is currently underway. "CHOP's extensive experience in gene therapy and cardiac research not only ensures the best outcomes for these patients but also brings hope for improved health and brighter futures," said Rossano. Greenberg et al. "Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease." N Engl J Med Online November 18, 2024. DOI: 10.1056/NEJMoa2412392. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Natalie Solimeo Children's Hospital of Philadelphia 267-426-6246 [email protected] SOURCE Children's Hospital of Philadelphia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

WATERTOWN, Mass.--( BUSINESS WIRE )--Nocion Therapeutics, Inc., a clinical stage biopharmaceutical company developing novel small molecule charged sodium channel blockers called “nocions”, that selectively silence actively firing nociceptors for the treatment of serious conditions involving cough, itch, and pain, today announced that the first patient has been dosed in the Phase 2b ASPIRE clinical trial of taplucainium for the treatment of chronic cough. ASPIRE is a Phase 2b, randomized, double-blind, placebo-controlled study investigating the efficacy, safety, and tolerability of Taplucainium Inhalation Powder (NOC-110) once daily in adults with refractory or unexplained chronic cough. Approximately 325 patients will be enrolled in the study at over 100 sites across the US, Canada, UK and Europe. “Dosing of the first patient in the ASPIRE clinical study is a significant milestone for Nocion,” said Rick Batycky, CEO of Nocion Therapeutics. “Taplucainium represents a novel approach to the treatment of chronic cough with the potential to deliver enhanced efficacy and reduced side effects to more than 8 million patients per year just in the United States.” ABOUT TAPLUCAINIUM Taplucainium (formerly NTX-1175) is a proprietary molecule in the novel class of charged sodium channel blockers that allows for specific silencing of activated/inflamed nociceptors while having minimal local off-target effects or systemic exposure. Unlike other investigative cough therapies, such as P2X3 antagonists, which target a specific large pore channel, taplucainium is formulated into a dry powder for inhalation, and once inhaled, gains access to the pulmonary nociceptors through any open large pore channel including P2X, TRPV and TRPA channels whereupon it inhibits the sodium channels responsible for initiating the pathological cough response. The broader mechanism of taplucainium should translate into an efficacious, long-lasting, antitussive that is fast acting in a number of cough conditions. Combined with good preliminary safety and efficacy data from earlier stage clinical work, this forms the basis for its use in cough indications beyond chronic cough. For more information, visit https://www.aspirechroniccoughstudy.com/#!/ ABOUT NOCION Nocion Therapeutics is a biopharmaceutical company developing novel small molecule charged sodium channel blockers called “nocions” that selectively affect actively firing nociceptors for the treatment of serious conditions involving cough, itch, and pain. The company’s mission is to safely alleviate suffering for millions of patients with conditions arising from activated sensory neurons. Working with Harvard’s Office of Technology Development, Nocion was founded on an exclusive license to foundational intellectual property from Harvard University and Boston Children’s Hospital. Venture investors in Nocion include Arkin Bio Capital, Canaan Partners, F-Prime Capital, Lumira Ventures, Mass General Brigham Ventures, Mission BioCapital, Monograph Capital, Morningside and Osage University Partners. For more information, visit: www.nociontx.com .

STAMFORD, Conn.--( BUSINESS WIRE )--GeneDx (Nasdaq: WGS), a leader in delivering improved health outcomes through genomic insights, today announced its scientific contributions at the 2024 American Society of Human Genetics (ASHG) annual meeting. GeneDx data will be presented across six platform presentations and five posters and will unveil findings from key research initiatives constructed on the backbones of its industry leading diverse dataset of more than 700,000 clinical exome and genomes. GeneDx leverages its database as a critical tool in a number of studies to drive transformational clinical care for pediatric patients as the industry continues to look for strong evidence to expand the utilization and clinical utility of genome sequencing. Through these strategic collaborations with SeqFirst, The University of Washington, PacBio the Autism Sequencing Consortium and GUARDIAN, GeneDx showcases the accessibility, affordability and actionability of exome and whole genome sequencing (WGS) in pediatric patients. Research to be presented this week at ASHG will include: Rapid whole genome sequencing (rWGS) in the NICU leads to changes in clinical care: In collaboration with SeqFirst, patient cases were analyzed when a diagnosis was found with rWGS to understand how decisions were made with genomic sequencing and what is missed in its absence when only using conventional care protocols. Racial disparities in an accurate genetic diagnosis: In one of the largest studies to look at ancestral backgrounds and genetic diagnosis, GeneDx, the University of Washington, and Geisinger explore the value of a diverse dataset to understand diagnostic yield and if it varies significantly based on ancestral background or if other factors are limiting access to a genetic diagnosis. Data validation for long read sequencing: With growing interest in the field to explore the clinical utility of long read sequencing, validation data will be presented assessing the sensitivity of PacBio’s HiFi long read sequencing to detect cases with a confirmed answer on short read whole genome sequencing (WGS) Additional cases where long read sequencing uncovered pathogenic variants that were difficult to detect on short read WGS will be presented. Genetic variants linked to Autism Spectrum Disorder (ASD): Working alongside the Autism Sequencing Consortium, research identifies 230 new genes associated with ASD. This molecular evidence underscores the effectiveness and accuracy of genetic diagnostics compared to current methods, which rely on parents’ or caregivers’ accounts of their child's development or professional observations of behavior. “The opportunity to present these findings at ASHG underscores GeneDx’s commitment to advancing genomic research to move forward its application in clinical settings,” said Dr. Paul Kruszka, MD, FACMG, Chief Medical Officer at GeneDx. “Our collaborations with leading research initiatives allow us to leverage our industry-leading dataset to drive innovation and improve patient outcomes. Across the board this work not only highlights the proven clinical utility of genomic testing but emphasizes the importance of equitable access.” GeneDx collaborated on the following: Presentations: Wednesday, November 6, 9:15 am MT: Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies. Janelle Stanton, PhD (University of Limerick, Ireland) - Room 505 Session 12 Thursday, November 7 at 1:30 pm MT: Use of exclusion criteria to select critically ill newborns for rapid genome sequencing captures precise genetic diagnoses missed by use of conventional inclusion criteria. Tara Wenger, MD, PhD (University of Washington) – Room 505 Session 54 Friday, November 8 at 10:45 am MT: Genome-wide profiling of highly similar paralogous genes using HiFi sequencing. Xiao Chen, PhD (PacBio) – Four Seasons Ballroom 4 Session 71 Friday, November 8 at 11:15 am MT: Benchmarking detection of technically challenging pathogenic variants with long-read sequencing and a head-to-head comparison with short-read sequencing in a clinical diagnostic laboratory. Joseph M. Devaney, PhD (GeneDx) – Four Seasons Ballroom 4 Session 71 Friday, November 8 at 1:45 pm MT: The largest to-date exome study of autism spectrum disorder triples the number of autism-associated genes. Frederick Satterstrom, PhD (Broad Institute) – Room 401 Session 78 Friday, November 8 at 6:00 pm MT: Expanded newborn screening using genome sequencing for early actionable conditions: results of the first 10,000 participants enrolled in the GUARDIAN study. Wendy Chung, MD, PhD (Boston Children’s Hospital) – Mile High Ballroom Session 86 Posters: Thursday, November 7 at 2:30 pm MT: Racial disparities in access to a precise genetic diagnosis are not due to differences in diagnostic yields. Jessica X. Chong, PhD (University of Washington) Thursday, November 7 at 2:30 pm MT: Partial methylation of a pathogenic XYLT1 repeat expansion associated with intrafamilial variation in severity of Desbuquois dysplasia 2. Michael J. Bamshad, MD (University of Washington) Friday, November 8 at 2:30 pm MT: Genetic etiologies and diagnostic yield of exome sequencing in pediatric motor speech disorders. Marissa Mitchel, MS (Geisinger Autism & Developmental Medicine Institute) Friday, November 8 at 2:30 pm MT: Evaluating dosage sensitivity predictions for multigenic copy number variants to facilitate clinical interpretation. Erin Riggs, MS (Geisinger) Friday, November 8 at 2:30 pm MT: De novo variants in GTF2H1 underlie variable syndromic developmental delay. Karynne Patterson, BS/BA (University of Washington) About GeneDx : GeneDx (Nasdaq: WGS) delivers personalized and actionable health insights to inform diagnosis, direct treatment, and improve drug discovery. The company is uniquely positioned to accelerate the use of genomic and large-scale clinical information to enable precision medicine as the standard of care. GeneDx is at the forefront of transforming healthcare through its industry-leading exome and genome testing and interpretation services, fueled by the world’s largest, rare disease data sets. For more information, please visit www.genedx.com and connect with us on LinkedIn , Facebook , and Instagram .