University of L'Aquila

Data published in the Cell Press Journal Molecular Therapy Nucleic AcidsGUILDFORD, United Kingdom, Sept. 18, 2023 (GLOBE NEWSWIRE) -- SiSaf Ltd, an RNA therapeutics company, is pleased to announce the publication in the peer-reviewed journal Molecular Therapy Nucleic Acids(1) of positive in vivo data demonstrating the safety and efficacy of its siRNA therapy for Autosomal Dominant Osteopetrosis 2 (ADO2). The data reported in the paper demonstrate that siRNA complexed with SiSaf’s silicon stabilized hybrid lipid nanoparticles (sshLNP) was able to significantly downregulate expression of an ADO2-specific mutant gene. These results could have significant translational impact on bone disease therapies and open the path to human trials of SiSaf’s potentially curative treatment for Osteopetrosis ADO2. There are currently no approved treatments for this debilitating disease and no other treatments currently in clinical trials. SIS-101-ADO, SiSaf’s lead in house program, is an ADO2-specific siRNA specifically designed against the human CLCN7G215R mRNA formulated with the company’s sshLNP. When tested via single intraperitoneal injection in pre-puberal ADO2 mice, carrying a heterozygous mutation of the Clcn7 gene (Clcn7G213R), SIS-101-ADO significantly downregulated the Clcn7G213R related mRNA levels in femurs at 48 h. Confirmatory results were observed at 2 weeks and 4 weeks after treatments (3 intraperitoneal injections/week), with rescue of the bone phenotype and demonstrating safety. The publication builds on data presented at the American Society of Bone and Mineral Research (ASBMR) 2022 Annual Meeting and is jointly authored by SiSaf and its collaborators from the University of L'Aquila, Italy, led by Professor Anna Maria Teti. Co-author on the paper, Dr. Suzanne Saffie-Siebert, CEO of SiSaf Ltd, said, “Targeting the bone safely and effectively is a challenge for RNA-based therapies. The in vivo data for our ADO2 treatment show that SiSaf’s silicon stabilized LNPs are able to deliver siRNA to the bone without any side effects. This is an important milestone on the path to clinical trials of SiSaf’s treatment for autosomal dominant Osteopetrosis type 2. And it could have wider translational significance for RNA-based treatments of other skeletal disorders.” Professor Anna Maria Teti added, “We can’t wait to see SIS-101-ADO used to treat ADO2 patients and look forward to further collaboration with SiSaf on potential therapies for other skeletal disorders.” SiSaf has had ongoing productive collaboration with Professor Teti’s group for over three years and continues to progress studies in support of its IND data package for SIS-101-ADO. During 2023 it successfully submitted an application to the U.S. FDA for Orphan Drug Designation for SIS-101-ADO which was granted in May. In addition, due to the serious manifestations of this rare skeletal disorder in children, the FDA granted SIS-101-ADO Rare Pediatric Disease Designation for the treatment of Autosomal Dominant Osteopetrosis. 1. Novel hybrid silicon-lipid nanoparticles deliver a siRNA to cure autosomal dominant osteopetrosis in mice. Implications for gene therapy in humans: Molecular Therapy Nucleic Acids: VOLUME 33, P925-937, SEPTEMBER 12, 2023, Antonio Maurizi et. al. https://doi.org/10.1016/j.omtn.2023.08.020 – ABOUT SISAF SiSaf is an RNA therapeutics company with a proprietary delivery platform. Its lead programs are a siRNA treatment for Osteopetrosis ADO2 and a partnered siRNA treatment for Corneal Dystrophy. The company is in the process of expanding its pipeline to other fields, including oncology. SiSaf’s proprietary Bio-Courier™ delivery platform uses silicon stabilized hybrid lipid nanoparticles (sshLNP) to improve the stability, safety, and transfection efficiency of RNA. sshLNP remove the need for an ultra-cold chain and unlike conventional lipid nanoparticles, they can be manufactured empty and the RNA can be introduced in a separate step. Led by founder and leading biomaterials specialist Dr. Suzanne Saffie-Siebert, SiSaf is a venture capital-backed private company. Headquartered in Guildford, UK, it has fully integrated research labs and bio-analytical facilities, a scalable technology to fast-track development, and a growing patent estate with extensive freedom to operate. To learn more, please visit www.sisaf.com Follow us on LinkedIn and Twitter. For further information please contact: MEDIA ENQUIRIES Scius communications Sue Charles – sue@sciuscommunications.com +44 7968726585 Katja Stout – katja@sciuscommunications.com +44 7789435990

The company prepares for bringing the wearable prescribed device to Europe next year NETANYA, Israel, Aug. 9, 2023 /PRNewswire/ -- Theranica, a prescribed digital therapeutics company developing advanced neuromodulation devices for migraine and other pain conditions, today announced it received expanded CE (Conformité Européenne) mark approval under MDR European regulation for Nerivio® as dual-use therapy for both acute and preventive treatment of migraine for adults and adolescents. The CE mark expansion for Nerivio is a critical milestone to accelerate the availability of the novel, drug-free migraine device into the European market. Migraine is a major global neurological disorder that affects over 1 billion people worldwide, with a prevalence higher than one in ten people in Europe. Research shows it's one of the most prevalent disorders, with a high morbidity, especially among young adults and females. Nerivio has been available with prescription in the USA since 2020, initially for acute treatment and since April this year also as a preventive treatment. "Migraine is the leading cause of disability worldwide, including for for adolescents and young adults, and early intervention with preventive treatment is necessary to restrain the disease from escalating", said Dr. Simona Sacco, Professor of Neurology at the University of L'Aquila, Italy, and second vice president of the European Headache Federation. "It is important to expand the treatment options with a non-pharmacological treatment, especially one that can both treat and prevent migraine." "With more than 50,000 prescribed Nerivio patients now in the US, we receive numerous requests, on a weekly basis, to bring the device to Europe," says Alon Ironi, CEO and co-founder of Theranica. "We have been waiting for the prevention indication approval, and with that are now preparing for making Nerivio available for people with Migraine in Europe starting 2024. Our focus is to empower underserved populations, particularly adolescents, to safely and effectively prevent and treat migraines, and be fully present in everyday life." Controlled by a smartphone app and self-administered, Nerivio wraps around the upper arm and uses sub-painful Remote Electrical Neuromodulation (REN) to activate nociceptive nerves fibers in arm to send signals which trigger a descending pain management mechanism in the brain called conditioned pain modulation (CPM), which turns off migraine pain and associated symptoms without medication. In simpler terms, the upper arm is stimulated to unleash a natural process in the brain to abort or relieve migraine headache and other associated symptoms. Each treatment lasts 45 minutes and is applied every other day for prevention or at the start of a migraine attack for acute treatment. About Theranica Theranica is a prescribed digital therapeutics company dedicated to creating effective, safe, affordable, low-side-effect therapies for idiopathic pain conditions. The company's award-winning flagship wearable, Nerivio®, is the first FDA-cleared and CE marked prescription migraine bioband for acute and/or preventive treatment of migraine with or without aura in people 12 years or older. Nerivio already serves more than 50,000 people with migraine in the USA, including adolescents and veterans. Theranica is expanding its proprietary technology to develop solutions for additional idiopathic pain conditions. Learn more by visiting our websites, theranica.com and nerivio.com, and following us on LinkedIn, Twitter, Instagram and Facebook. Theranica Contact Ronen Jashek [email protected] +972-72-390-9750 Media Contact V.A. Lopes Grey Matter Marketing [email protected] SOURCE Theranica

Hydrogen, the most abundant element in the universe, is found everywhere from the dust filling most of outer space to the cores of stars to many substances here on Earth. This would be reason enough to study hydrogen, but its individual atoms are also the simplest of any element with just one proton and one electron. Hydrogen, the most abundant element in the universe, is found everywhere from the dust filling most of outer space to the cores of stars to many substances here on Earth. This would be reason enough to study hydrogen, but its individual atoms are also the simplest of any element with just one proton and one electron. For David Ceperley, a professor of physics at the University of Illinois Urbana-Champaign, this makes hydrogen the natural starting point for formulating and testing theories of matter. Ceperley, also a member of the Illinois Quantum Information Science and Technology Center, uses computer simulations to study how hydrogen atoms interact and combine to form different phases of matter like solids, liquids, and gases. However, a true understanding of these phenomena requires quantum mechanics, and quantum mechanical simulations are costly. To simplify the task, Ceperley and his collaborators developed a machine learning technique that allows quantum mechanical simulations to be performed with an unprecedented number of atoms. They reported in Physical Review Letters that their method found a new kind of high-pressure solid hydrogen that past theory and experiments missed. "Machine learning turned out to teach us a great deal," Ceperley said. "We had been seeing signs of new behavior in our previous simulations, but we didn't trust them because we could only accommodate small numbers of atoms. With our machine learning model, we could take full advantage of the most accurate methods and see what's really going on." Hydrogen atoms form a quantum mechanical system, but capturing their full quantum behavior is very difficult even on computers. A state-of-the-art technique like quantum Monte Carlo (QMC) can feasibly simulate hundreds of atoms, while understanding large-scale phase behaviors requires simulating thousands of atoms over long periods of time. To make QMC more versatile, two former graduate students, Hongwei Niu and Yubo Yang, developed a machine learning model trained with QMC simulations capable of accommodating many more atoms than QMC by itself. They then used the model with postdoctoral research associate Scott Jensen to study how the solid phase of hydrogen that forms at very high pressures melts. The three of them were surveying different temperatures and pressures to form a complete picture when they noticed something unusual in the solid phase. While the molecules in solid hydrogen are normally close-to-spherical and form a configuration called hexagonal close packed -- Ceperley compared it to stacked oranges -- the researchers observed a phase where the molecules become oblong figures -- Ceperley described them as egg-like. "We started with the not-too-ambitious goal of refining the theory of something we know about," Jensen recalled. "Unfortunately, or perhaps fortunately, it was more interesting than that. There was this new behavior showing up. In fact, it was the dominant behavior at high temperatures and pressures, something there was no hint of in older theory." To verify their results, the researchers trained their machine learning model with data from density functional theory, a widely used technique that is less accurate than QMC but can accommodate many more atoms. They found that the simplified machine learning model perfectly reproduced the results of standard theory. The researchers concluded that their large-scale, machine learning-assisted QMC simulations can account for effects and make predictions that standard techniques cannot. This work has started a conversation between Ceperley's collaborators and some experimentalists. High-pressure measurements of hydrogen are difficult to perform, so experimental results are limited. The new prediction has inspired some groups to revisit the problem and more carefully explore hydrogen's behavior under extreme conditions. Ceperley noted that understanding hydrogen under high temperatures and pressures will enhance our understanding of Jupiter and Saturn, gaseous planets primarily made of hydrogen. Jensen added that hydrogen's "simplicity" makes the substance important to study. "We want to understand everything, so we should start with systems that we can attack," he said. "Hydrogen is simple, so it's worth knowing that we can deal with it." This work was done in collaboration with Markus Holzmann of Univ. Grenoble Alpes and Carlo Pierleoni of the University of L'Aquila. Ceperley's research group is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Computational Materials Sciences program under Award DE-SC0020177.