DYN-201

STRASBOURG, France and PHILADELPHIA, Jan. 26, 2021 /PRNewswire/ -- Dynacure, a clinical-stage company focused on developing and commercializing novel therapies to transform the lives of patients with rare diseases who have limited or no treatment options, announced today that the U.S. Patent and Trademark Office (USPTO) has granted U.S. Patent No. US 10, 865, 414 related to DYN101, an investigational antisense product candidate designed to reduce the expression of dynamin 2 protein (DNM2), for the treatment of Myotubular and Centronuclear Myopathies (CNM). The U.S. patent is part of a patent family, exclusively licensed from Ionis Pharmaceuticals, which covers modulators of DNM2 expression. This patent family includes one additional U.S. pending application and one European application and 18 other foreign pending applications (Australia, Brazil, Canada, Chili, China, Colombia, Israel, India, Japan, Korea, Mexico, Malaysia, New-Zealand, Peru, Russia, Singapore, South Africa and Taiwan). Patents issuing from the pending applications in this family, if any, are expected to expire in 2039, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. "Today, there are no FDA- or EMA-approved medicines to treat the underlying cause of CNM. We believe that using an antisense oligonucleotide to modulate the disease-driving protein, DNM2, is the preferred modality to provide therapeutic benefit to patients," said Frederic Legros, Chief Operating Officer of Dynacure. "Designing and developing the right therapy with the potential to reverse the progression of disease has been an important challenge, which required the expertise of our strategic partner, Ionis Pharmaceuticals. We are pleased to expand our IP footprint with today's grant for DYN101 in the United States, which if approved, could provide the first disease-modifying treatment for a majority of patients living with CNM." The U.S. patent announced today expands Dynacure's existing intellectual property estate covering claims to modulate the DNM2 protein for the treatment of CNM, which includes four issued patents in the U.S., China, Europe and Japan, one U.S. pending application, and five foreign pending applications in Australia, Brazil, Canada, India, and Japan. About Myotubular and Centronuclear Myopathies Myotubular and Centronuclear Myopathies (CNM) are serious, rare, life-threatening disorders that affect skeletal muscles from birth. CNM derives its name based on the central location of the muscle fiber nucleus, which is an abnormal finding observed in muscle biopsies. People with CNM begin experiencing muscle weakness at any time from birth to early adulthood and many patients die within the first 18 months of life. Patients who survive longer require intense medical management and nearly uninterrupted support, including permanent ventilation, brace with head support and feeding tubes. The disease is driven by mutations in multiple genes including MTM1, DNM2 and BIN1 and Dynacure scientists have discovered a link between an increase in DNM2 protein and the direct cause of the disease 4. The three classical forms of CNM are X-linked myotubular myopathy (XLCNM), autosomal dominant CNM (ADCNM), and autosomal recessive CNM (ARCNM), which are all associated with poor prognosis. Myotubular and Centronuclear Myopathies affect an estimated 4,000 to 5,000 patients in the European Union, United States, Japan and Australia1. About DYN101 DYN101, an investigational antisense oligonucleotide product candidate using Ionis Pharmaceuticals' proprietary antisense technology, is designed to reduce the expression of dynamin 2 protein (DNM2) for the treatment of Myotubular and Centronuclear Myopathies (CNM). Preclinical studies have shown that DYN101 has the potential to be disease modifying in CNM, with preclinical activity observed in animal models of XLCNM and ADCNM 2,3 . Prevention and reversion of the disease was observed with a dose-dependent improvement in whole body strength and mice survival. The development plan for DYN101 was designed to be broad and it is the only known program investigating a treatment for the majority CNM populations, comprised of those who have XLCNM or ADCNM. DYN101 is currently under clinical investigation in several European countries. DYN101 has been granted Orphan Drug designations by the U.S. FDA and EMA and rare pediatric disease designation by the FDA. About Dynacure Dynacure is a clinical-stage company focused on developing and commercializing novel therapies to transform the lives of patients with rare diseases who have limited or no treatment options. The Dynacure team leverages its proven track record in rare disease drug development to build a pipeline of novel drug candidates. Dynacure is developing DYN101, an investigational antisense product candidate designed to reduce the expression of dynamin 2 protein for the treatment of Myotubular and Centronuclear Myopathies, in strategic collaboration with Ionis Pharmaceuticals. Dynacure is also building a complementary research portfolio targeting other orphan disorders, including its DYN201 program for the treatment of Hereditary Spastic Paraplegias (caused by mutations in the SPG11 gene). Dynacure is headquartered in Strasbourg, France with a corporate office in Philadelphia, PA, USA. Dynacure's investors include Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Idinvest, Ionis Pharmaceuticals, Kurma Partners, Perceptive Advisors, Pontifax and funds managed by Tekla Capital Management LLC. For more information, please visit . 1. Neuromuscul Disord. 2018 Sep;28(9):766-777. doi: 10.1016/j.nmd.2018.06.012. Epub 2018 Jul 2. Nat Commun. 2017 Jun 7;8:15661. doi: 10.1038/ncomms15661. 3. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11066-11071. doi: 10.1073/pnas.1808170115. Epub 2018 Oct 4. (Cowling et al 2014 JCI) View original content to download multimedia: SOURCE Dynacure

STRASBOURG, France and PHILADELPHIA, Jan. 15, 2021 /PRNewswire/ -- Dynacure, a clinical-stage company focused on developing and commercializing novel therapies to transform the lives of patients with rare diseases who have limited or no treatment options, announced the publication of a paper entitled, Hierarchical Bayesian modelling of disease progression to inform clinical trial design in centronuclear myopathy (CNM). The paper was published this month in Orphanet Journal of Rare Diseases, a scientific, peer-reviewed publication and can be accessed here. CNM is a group of rare and severe neuromuscular diseases that result from genetic mutations that impair the function of protein within muscle cells. People with CNM begin experiencing muscle weakness at any time from birth to early adulthood and many patients die within the first 18 months of life. Patients who survive longer require intense medical management and nearly uninterrupted support, including permanent ventilation, brace with head support and feeding tubes. There is currently no FDA- or EMA-approved therapeutic treatment for CNM. "There are profound and urgent needs that exist within the CNM patient community, but as with most rare diseases, the clinical variability and genetic heterogeneity of CNM result in major challenges in clinical trial design," said Laurent Servais, M.D, Professor of Pediatric Neuromuscular Diseases, MDUK Oxford Neuromuscular Center, Department of Pediatrics at the University of Oxford. "We must continue to look for innovative ways to thoughtfully conduct clinical trials in small and severely affected disease populations with urgent medical needs and I believe we have successfully developed an innovative method to approach the challenges in clinical trial design." The Hierarchical Bayesian model used prospective, multicenter natural history and 4-year follow-up data from 59 patients carrying mutations in the MTM1 or DNM2 genes, which are the primary mutations that cause CNM. Each patient's own natural history study data was used to predict progression in the absence of treatment, simulate the evolution of symptoms for individual patients over time, and compare these simulated trajectories with post-treatment outcomes. The Bayesian model was designed by Pharmalex, a global leader in innovative clinical trial design and statistics. "Bayesian statistics offer the opportunity to compare the outcomes of patients at a given time after treatment to the simulated endpoint scores at the same given time without a treatment," said Brad Carlin, Senior Advisor, Statistics and Data Science at Pharmalex. "This approach allowed us to predict an individual patient trajectory with a certain probability and to estimate the probability that an observed deviation from that predicted trajectory would have happened without intervention." "We believe that the Bayesian model as applied to CNM with the use of natural history is encouraging and worthy of further exploration among the treatment community," said Leen Thielemans, Chief Development Officer at Dynacure. "We are tremendously grateful to the patient community for participating in the natural history study, which was led by the Institute of Myology in Paris, for their valuable contribution to our continued understanding of CNM." About PharmaLex PharmaLex is a leading provider of specialised services for the pharma, biotech and medical device industries. We guide you from early strategic planning activities and non-clinical requirements through clinical development, regulatory submission processes and post-approval / maintenance post-launch activities. Our experts use technology-enabled solutions to support you through the entire product lifecycle. We deliver exceptional results — going above and beyond the standard to deliver tailor-made solutions worldwide. The PharmaLex Group now has over 1300 employees, with 34 offices in 21 countries and more than 600 satisfied clients worldwide. About Myotubular and Centronuclear Myopathies Myotubular and Centronuclear Myopathies (CNM) are serious, rare, life-threatening disorders that affect skeletal muscles from birth. CNM derives its name based on the central location of the muscle fiber nucleus, which is an abnormal finding observed in muscle biopsies. People with CNM begin experiencing muscle weakness at any time from birth to early adulthood and many patients die within the first 18 months of life. Patients who survive longer require intense medical management and nearly uninterrupted support, including permanent ventilation, brace with head support and feeding tubes. The disease is driven by mutations in multiple genes including MTM1, DNM2 and BIN1 and Dynacure scientists have discovered a link between an increase in DNM2 protein and the direct cause of the disease4. The three classical forms of CNM are X-linked myotubular myopathy (XLCNM), autosomal dominant CNM (ADCNM), and autosomal recessive CNM (ARCNM), which are all associated with poor prognosis. Myotubular and Centronuclear Myopathies affect an estimated 4,000 and 5,000 patients in the European Union, United States, Japan and Australia 1. About DYN101 DYN101, an investigational antisense oligonucleotide product candidate using Ionis Pharmaceuticals' proprietary antisense technology, is designed to reduce the expression of dynamin 2 protein (DNM2) for the treatment of Myotubular and Centronuclear Myopathies (CNM). Preclinical studies have shown that DYN101 has the potential to be disease modifying in CNM, with preclinical activity observed in animal models of XLCNM and ADCNM2,3. Prevention and reversion of the disease was observed with a dose-dependent improvement in whole body strength and mice survival. The development plan for DYN101 was designed to be broad and it is the only known program investigating a treatment for the majority CNM populations, comprised of those who have XLCNM or ADCNM. DYN101 is currently under clinical investigation in several European countries. DYN101 has been granted Orphan Drug designations by the U.S. FDA and EMA and rare pediatric disease designation by the FDA. About Dynacure Dynacure is a clinical-stage company focused on developing and commercializing novel therapies to transform the lives of patients with rare diseases who have limited or no treatment options. The Dynacure team leverages its proven track record in rare disease drug development to build a pipeline of novel drug candidates. Dynacure is developing DYN101, an investigational antisense product candidate designed to reduce the expression of dynamin 2 protein for the treatment of Myotubular and Centronuclear Myopathies, in strategic collaboration with Ionis Pharmaceuticals. Dynacure is also building a complementary research portfolio targeting other orphan disorders, including its DYN201 program for the treatment of Hereditary Spastic Paraplegias (caused by mutations in the SPG11 gene). Dynacure is headquartered in Strasbourg, France with a corporate office in Philadelphia, PA, USA. Dynacure's investors include Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Idinvest, Ionis Pharmaceuticals, Kurma Partners, Perceptive Advisors, Pontifax and funds managed by Tekla Capital Management LLC. For more information, please visit . 1. Neuromuscul Disord. 2018 Sep;28(9):766-777. doi: 10.1016/j.nmd.2018.06.012. Epub 2018 Jul 2. Nat Commun. 2017 Jun 7;8:15661. doi: 10.1038/ncomms15661. 3. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11066-11071. doi: 10.1073/pnas.1808170115. Epub 2018 Oct 4. (Cowling et al 2014 JCI)