Phelan-McDermid syndrome

LONDON, Feb. 15, 2024 /PRNewswire/ -- AMO Pharma Limited ("AMO Pharma"), a privately held clinical-stage specialty biopharmaceutical company focusing on rare genetic disorders with limited or no treatment options, today announced a collaboration with Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences in Canada, to advance a clinical proof of concept trial to assess the efficacy of AMO-02 (tideglusib), AMO Pharma's investigational oral glycogen synthase kinase 3 beta (GSK3β) inhibitor, in the treatment of genotype positive arrhythmogenic cardiomyopathy (ACM). The study, entitled "Targeted Therapy with Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy" (TaRGET), will be led by the research team at PHRI and will involve collaboration with multiple organizations in addition to AMO Pharma including the Hearts in Rhythm Organization (HiRO). Enrollment is set to begin in mid-2024 at 20 sites across Canada and will include a total of 120 participants who will be randomized in a 1:1 ratio. "It can be a helpless feeling to carry a gene for ACM and know that, no matter how you live your life, you may someday develop a deadly form of heart disease," said Jason Roberts, scientist at PHRI and TaRGET study principal investigator, adding, "Encouraged by earlier studies in animal models, we are hopeful that tideglusib may serve as an effective treatment that can dramatically improve the health of people living with ACM. The TaRGET trial is a critical first step in evaluating this potential." ACM is a form of genetic heart disease characterized by scarring in the heart muscle. This scarring increases the risk of dangerously fast heart rhythms that can lead to sudden cardiac death (SCD). There are currently no approved medical therapies that have been shown to prevent progression of ACM. An implantable cardioverter defibrillator (ICD) is recommended for prevention of SCD for ACM patients considered at high risk for SCD. In prior research, a high-throughput screen of bioactive compounds against a zebrafish model of ACM identified a small molecule classified as a GSK3β inhibitor that successfully prevented and rescued the phenotype, findings that have subsequently been reproduced in a series of ACM murine models. GSK3β is an enzyme that modulates the activity of a broad spectrum of intracellular signaling pathways, including the canonical Wnt/β-catenin pathway whose suppression has been suggested to exert an important role in ACM pathogenesis. "As we continue to advance our research to assess the potential benefits of AMO-02 in the treatment of myotonic dystrophy, we are very pleased to be supporting this landmark research effort in ACM with the outstanding team at PHRI," said Mike Snape, chief scientific officer at AMO Pharma. "Based on extensive research that highlights the proven MOA of AMO-02 as a clinically safe and well tolerated GSK3β inhibitor, we look forward to progress in advancing this promising program that can bring new hope to people living with ACM and their families in the years ahead. This new data has the potential to build on the cardiac efficacy data previously reported in studies conducted in Duchenne muscular dystrophy by Professor Val Fajardo's team at Brock University." About AMO Pharma AMO Pharma is a clinical-stage specialty biopharmaceutical company working to identify and advance promising therapies for the treatment of serious and debilitating diseases in patient populations with significant areas of unmet need, including rare and severe childhood onset neurogenetic disorders with limited or no treatment options. In addition to developing AMO-02 for myotonic dystrophy, the company is also progressing AMO-01 as a clinical stage treatment for Phelan-McDermid syndrome and AMO-04 as a clinic-ready potential medicine for Rett syndrome and related disorders. AMO-02, AMO-01 and AMO-04 are investigational medicines that have not yet been approved for the treatment of patients anywhere in the world. Advice provided to AMO Pharma by regulators is under the condition that any scientific advice given is not legally binding with regards to any future application for the product concerned, neither on the part of MHRA/Commission on Human Medicines (CHM) nor on the Company. Furthermore, advice cannot be taken as indicative of any future agreed position. For more information, please visit the AMO Pharma website at . Media Contact Holly Stevens Berry & Company Public Relations 212 253 8881 [email protected] Logo -

Initial study will focus on adults with disease; company plans to initiate Phase I clinical trials in the U.S. in 2H2024 Preclinical studies in rodents and NHPs demonstrated improvement in neurobehavioral, cognitive and motor functional abnormalities: JAG201 delivers a functional SHANK3 gene directly into the CNS via the AAV9 vector to treat the root cause of the disease There are currently no treatments for the ~30,000 individuals in the U.S. with autism or Phelan-McDermid syndrome, where a SHANK3 mutation or deletion is present LAKE FOREST, Ill.--(BUSINESS WIRE)-- Jaguar Gene Therapy a biotechnology company accelerating breakthroughs in gene therapy for patients suffering from severe genetic diseases, including those that affect sizeable patient populations, today announced the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) Application for JAG201, a gene therapy for a genetic form of autism spectrum disorder (ASD) and Phelan-McDermid syndrome (PMS). There are currently no treatments for the ~30,000 individuals in the U.S. with ASD or PMS where a SHANK3 mutation or deletion is present. JAG201 aims to deliver functional SHANK3 via the AAV9 vector to treat the root cause of the disease. Preclinical studies in rodents and non-human primates (NHP) demonstrated that functional SHANK3 delivery leads to improvements in neurobehavioral, cognitive and motor function abnormalities. The company plans to initiate a Phase I trial in adults with ASD or PMS where a SHANK3 mutation or deletion is present in the United States in the second half of the year. “We are pleased to receive FDA clearance to bring our investigational SHANK3 gene therapy to the clinic. The pre-clinical data indicate that JAG201 may have the potential to be transformative for those suffering with the disorder,” said Joe Nolan, chief executive officer of Jaguar Gene Therapy. “This is a significant milestone for our company but more importantly for the approximately 30,000 individuals living with a genetic form of autism or Phelan-McDermid syndrome who can suffer from a range of clinical manifestations, including global developmental delay, impaired speech and communication, and worsening cognitive, social and motor function disability that ultimately requires 24-hour care and supervision. Currently, there are no treatment options to address the root cause – we hope to change that.” “As a clinician working directly with individuals living with SHANK3 haploinsufficiency and their families, I recognize deeply the profound challenges faced every single day,” said Alexander Kolevzon, M.D., professor of Psychiatry and Pediatrics at the Icahn School of Medicine at Mount Sinai. “The interventions we offer can certainly help but, frankly, they’re inadequate. My patients and all those with SHANK3 haploinsufficiency deserve a treatment option that addresses the underlying biology.” SHANK3 haploinsufficiency leads to synaptic dysfunction, disrupting communication between nerve cells. It causes a reduction of several key receptors and signaling proteins at excitatory synapses, resulting in impaired synaptic formation and function. Adequate synapse function is an essential prerequisite of all neuronal processing, including higher cognitive functions and learning. JAG201 delivers a functional SHANK3 minigene via an adeno-associated virus serotype 9 (AAV9) vector to target neurons in the central nervous system. The therapy is administered via a one-time unilateral intracerebroventricular (ICV) injection, targeting the entire brain and spinal cord. JAG201 is designed to transduce haploinsufficient neurons, to provide proper SHANK3 levels, and to durably restore the synaptic function required for learning and memory, which underlie appropriate neurodevelopment and maintenance of cognitive, communicative, social and motor skills. The program is exclusively licensed from Broad Institute of MIT and Harvard, and based on the groundbreaking work of Guoping Feng, Ph.D. “My lab has focused on studying the molecular mechanisms regulating the development and function of synapses in the brain, including the role of SHANK3, because we believe the potential to address synaptic dysfunction could positively transform the lives of so many with neurodevelopmental disorders,” said Dr. Feng, Institute member of the Broad Institute and a senior scientist and director of model systems and neurobiology in the Broad's Stanley Center for Psychiatric Research, the Poitras Professor of Brain and Cognitive Sciences at MIT, associate director of the McGovern Institute, and a member of the Yang Tan Collective at MIT. “Having directly generated promising preclinical data in rodent and non-human primate models of SHANK3 insufficiency, thereby reducing the risk of the translational potential of JAG201, I am very excited to now follow Jaguar as they progress into the clinic with JAG201.” SHANK3 haploinsufficiency causes PMS (also known as 22q13.3 deletion syndrome), a rare genetic disorder with an estimated prevalence of 1 in 10,000.1,2 Genetic sequencing studies indicate that SHANK3 mutations may be present in approximately 1% of patients with ASD, equating to around 30,000 patients in the U.S., although this estimate is perceived as low by clinical experts given the barriers of access and low adoption of genetic testing in the diagnostic journey of ASD.3,4 In the subset of ASD patients that also have moderate to profound intellectual disability (ID), the prevalence of SHANK3 mutations increases from approximately 1% to 2.12%.3,5 An Externally Led Patient Focused Drug Development (EL-PFDD) Meeting on PMS was held with the FDA in November 2022, hosted by CureSHANK and co-planned with the Phelan-McDermid Syndrome Foundation (PMSF). Key insights from the meeting include: PMS has severe quality of life impacts on those living with the disease, as well as on parents and siblings; PMS has an overwhelming unmet medical need; and existing therapies and medical treatments are not very effective.6 “As an organization dedicated to expediting life-changing therapies for Phelan-McDermid syndrome, we are thrilled for JAG201 to be cleared for clinical trials,” said Geraldine Bliss, founder and president of CureSHANK. “I understand first-hand as the parent of a young adult with Phelan-McDermid syndrome the dearth of available therapies and the incredible potential of a treatment that addresses the root cause of this severe and pervasive disease.” “Families deserve and are desperately waiting for treatments to address Phelan-McDermid syndrome, and we are very excited the FDA has cleared JAG201 for clinical trials,” said Ronni Blumenthal, CEO of the Phelan-McDermid Syndrome Foundation. “Members of our community are eager to have treatment options that could potentially lessen or eliminate even just one or two of the devastating symptoms of the disease, if not more, to positively improve the lives of our loved ones.” About Jaguar Gene Therapy Jaguar Gene Therapy, LLC is a clinical stage biotechnology company dedicated to accelerating breakthroughs in gene therapy for patients suffering from severe genetic diseases including those that impact sizeable patient populations. The company is made up of a proven team of experts who have first-hand experience in bringing novel gene therapy treatments to patients and their families. Jaguar is rapidly advancing an initial pipeline of three programs. The company’s lead IND-cleared program targets severe neurodevelopmental disorders caused by mutations or deletions in SHANK3 including a genetic form of autism spectrum disorder and Phelan-McDermid syndrome. The second pipeline program targets Type 1 galactosemia and the third targets Type 1 diabetes. Jaguar partners with Advanced Medicine Partners, soon to be spun out from Jaguar, to manufacture its therapeutics. Jaguar’s key investors include Deerfield Management Company, ARCH Venture Partners and Eli Lilly and Company. For more information, please visit and follow Jaguar Gene Therapy on LinkedIn. References 1. Costales JL et al. Neurotherapeutics 2015; 12 (3): 620–630. 2. What is Phelan-McDermid syndrome? Available at: . Accessed January 2023. 3. Betancur C et al. Mol Autism 2013; 4 (1): 17. 4. Jaguar Gene Therapy market research, 2022; data on file. 5. Leblond CS et al. PLoS Genet 2014; 10 (9): e1004580. 6. Phelan-McDermid Voice of the Patient Report. Available at: . Accessed January 2024. Disclosure Dr. Alexander Kolevzon has served as a paid consultant for Jaguar Gene Therapy.

26 different customers representing North America, Asia and Europe 33 oral presentations across four consecutive days 69 scientific posters will be featured in a virtual exhibition hall Topics span the application of optical genome mapping (OGM) in research applications in cancer, cell and gene therapy, and genetic diseases SAN DIEGO, Jan. 19, 2024 (GLOBE NEWSWIRE) --Bionano Genomics, Inc (Nasdaq: BNGO) today announced its 2024 Symposium lineup of 33 oral presentations delivered by 26 different customers worldwide featuring the utility of optical genome mapping (OGM) across a wide range of research applications in cancer, cell and gene therapy, and genetic disease. 2024 Symposium will take place virtually from January 22 to 25, 2024. During these four days, customers will showcase their latest research findings using OGM. Each day will feature user presentations, a live panel with Q&A, and scientific posters within the virtual exhibition hall. On day 2, Bionano will unveil a new product expected to advance cytogenetics and structural variant analysis. “We believe 2024 Symposium is an opportunity for the OGM community to come together and share the progress they are making in translational research using OGM alongside other genome analysis tools,” said Erik Holmlin, PhD, president and chief executive officer of Bionano Genomics. “Symposium provides a chance for anyone interested or currently working with OGM to form connections within the community and see the potential impact of looking at the genome in a different way. We believe this year’s event will be our best to date, with an expanded focus on the use of OGM in cell and gene therapy, as well as some very exciting product announcements that will drive further research advancements.” “Our 2023 Symposium was a fantastic event where OGM users shared their data covering genetic disorder and cancer research. Since then, we have made significant improvements in our end-to-end workflow which we believe has enabled our customers to advance their clinical and translational research. The presentations at this year’s event have been elevated to a new level, with dedicated sessions on advancements in heme malignancy research and solid tumor analysis, updates from global consortia driving OGM adoption, and new OGM data from researchers focused on solving constitutional diseases and rare disease,” said Alka Chaubey, PhD, FACMG, chief medical officer at Bionano. “Symposium attendees have a unique opportunity to learn from their peers, network, and view scientific posters and new products that we will showcase each day.” Each session of Symposium will start at 7:00 am PST and will last approximately 3 hours. After the scientific presentations, the speakers will join for a live panel discussion and Q&A moderated by Dr. Chaubey. In addition, each day will feature a scientific poster exhibit. Below is the list of customer presentations for each day and the application area. January 22: New Standards in Hematological Malignancies Speaker Institution Title Dr. Tiffany Clouston Saint John Regional Hospital Optical Genome Mapping: Pivoting Towards a New Technology Dr. Ying Zou Johns Hopkins University School of Medicine Comprehensive Genome-wide Genetic Pro Plasma Cell Neoplasm by OGM Dr. Guilin Tang University of Texas MD Anderson Cancer Center Optical Genome Mapping (OGM) in T-lymphoblastic Leukemia (T-ALL) Dr. Yanming Zhang Memorial Sloan Kettering Cancer Center Clinical Research Applications of Optical Genome Mapping (OGM) in Cancer Cytogenetics Dr. Agnes Daudignon Lille Hospital FrOGG: French Speaking OGM Group from GFCH Dr. Adam Smith University of Toronto The "Framework" for the Clinical Research Implementation of Optical Genome Mapping in Hematologic Malignancies Daniel Saul Bionano Advancements in Informatics and Software for OGM Data Analysis January 23: New Frontiers in Oncology Speaker Institution Title Dr. Marc-Henri Stern Institut Curie Features of Homologous Recombination Deficiency (HRD) in Solid Tumors Using Optical Genome Mapping Dr. Isabelle Raymound-Bouchard Hôpital Maisonneuve-Rosemont Developing Optical Genome Mapping for CD 138+ Plasma Cells Dr. Scott Ryall Brigham and Women’s Hospital Illuminating a New Path Forward for Cancer Research Dr. Ravindra Kolhe Augusta University Novel Biomarkers Unveiled by Utilization of OGM in Cancer Investigations Dr. Trilochan Sahoo Bionano Laboratories A Prospective Study of Optical Genome Mapping in Hematologic Malignancies Dr. Deb Tweddle Newcastle University Novel Structural Variants Detected by Optical Genome Mapping in Neuroblastoma Dr. Miriam Bornhorst Lurie Children’s Hospital of Chicago Application of Optical Genome Mapping for Pediatric Brain Tumors: Solving Challenging Cases Dr. Adrian Dubuc Roswell Park Comprehensive Cancer Center Raising the Bar: Comprehensive Cytogenetic Profiling for Improved Lymphoma Analysis Darisha Jiandani Bionano The Next Major OGM Advancement: Unlocking Flexible Structural Variant Analysis at Scale January 24: Advances in Constitutional Applications Speaker Institution Title Dr. Roger Stevenson Equinamitas Optical Genome Mapping for Prenatal Genetic Testing – Multisite Evaluation and Validation Dr. Roger Stevenson Equinamitas Detection of Constitutional Structural Variants by Optical Genome Mapping – A Multisite Study of Postnatal Samples Dr. Nikhil Sahajpal Greenwood Genetic Center Optical Genome Mapping in Rare Disorders Dr. Noemi Buisset Medicover Genetics Insights from Optical Genome Mapping: Uncovering Discrepancies in Chorionic Villi STC and LTC Dr. Laila El Khattabi AP-HP Sorbonne The CHROMAPS study: First Results from Optical Genome Mapping Dr. Maria Clara Bonaglia Scientific Institute E. Medea Optical Genome Mapping (OGM): Refining Genotype Phenotype Correlation in Different Types of Structural Variants Dr. Yassmine Akkari Nationwide Children’s Hospital Optical Genome Mapping (OGM) Identifies Multiple Structural Variants in a Case with Atypical Phelan-McDermid Syndrome  Dr. Ulrich Brockel Medical College of Wisconsin Optical Genome Mapping for Constitutional Chromosome Analysis Dr. Madhuri Hedge Revvity Molecular Analysis of Facioscapulohumeral Muscular Dystrophy Using Optical Genome Mapping Tanushi Sahai Bionano The Sample Preparation Landscape for Optical Genome Mapping January 25: OGM in Cell and Gene Therapy Speaker Institution Title Dr. Alex Hastie Bionano Detection of CRISPR Related Structural Variants in Genome Edited Hematopoietic Stem Cells in X-SCID Disease Dr. Sam Dougaparsad Bionano Optical Genome Mapping: Revolution in Quality Control for Cell Genomic Integrity Dr. John Yu Chang Gung Memorial Hospital Whole Genomic Analysis Reveals Atypical Non-Homologous Off-target Large Structural Variants Induced by CRISPR-Cas9-mediated Genome Editing Dr. Samantha Maragh National Institute of Standards and Technology Initial Outcomes of Variant Detection and Quantitation from the First NIST Genome Editing Consortium Interlab Study Dr. Andy Pang Bionano Genome Integrity QC Using Optical Genome Mapping – A Technical Guide Owen Pearce eGenesis Engineering Porcine Genomes for Xenotransplantation: Detecting Structural Variants in Engineered Genomes Using Optical Genome Mapping Dr. Saumyaa Saymyaa AstraZeneca Applications of OGM in Cell and Gene Therapy Symposium registration is open to all and there is no charge for attending this event. Register today at . About Bionano Bionano is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Company’s mission is to transform the way the world sees the genome through OGM solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. Through its Lineagen, Inc. d/b/a Bionano Laboratories business, the Company also provides diagnostic testing for patients with clinical presentations consistent with autism spectrum disorder and other neurodevelopmental disabilities. The Company also offers an industry-leading, platform-agnostic software solution, which integrates next-generation sequencing and microarray data designed to provide analysis, visualization, interpretation and reporting of copy number variants, single-nucleotide variants and absence of heterozygosity across the genome in one consolidated view. The Company additionally offers nucleic acid extraction and purification solutions using proprietary isotachophoresis technology. For more information, visit or Unless specifically noted otherwise, Bionano’s OGM products are for research use only and not for use in diagnostic procedures. Forward-Looking Statements of Bionano This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believe,” “potential,” “will” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances and the negatives thereof) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the anticipated benefits of the 2024 Symposium, the potential for OGM to be adopted for applications discussed at the 2024 Symposium, and the ability and utility of OGM to be adopted for applications in genetic disease and cancer research and for cell and gene therapy and other applications discussed at the 2024 Symposium. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of geopolitical and macroeconomic developments, such as recent and future bank failures, the ongoing Ukraine-Russia conflict, related sanctions, the Israel-Hamas war, and any global pandemics, on our business and the global economy; challenges inherent in developing, manufacturing and commercializing products; our ability to further deploy new products and applications and expand the markets for our technology platforms; changes in the competitive landscape and the introduction of competitive technologies or improvements to existing technologies; failure of future study results to support those reported and discussed at the 2024 Symposium; future study results that contradict the results discussed and reported at the 2024 Symposium; failure of OGM to be adopted for applications in genetic disease and cancer research and for cell and gene therapy and other applications discussed at the 2024 Symposium; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; and the risks and uncertainties associated with our business and financial condition in general; our expectations and beliefs regarding future growth of the business and the markets in which we operate; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts and our ability to continue as a “going concern”; and including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2022 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. We are under no duty to update any of these forward-looking statements after the date they are made to conform these statements to actual results or revised expectations, except as required by law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date the statements are made. Moreover, except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements contained in this press release. CONTACTS Company Contact: Erik Holmlin, CEO Bionano Genomics, Inc. +1 (858) 888-7610 eholmlin@bionano.com Investor Relations: David Holmes Gilmartin Group +1 (858) 888-7625 IR@bionano.com