Osteopetrosis Autosomal Dominant Type 2

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

GUILDFORD, England, May 15, 2023 (GLOBE NEWSWIRE) -- SiSaf Ltd, an RNA delivery and therapeutics company, announces that SIS-101-ADO, its siRNA therapeutic for patients with Autosomal Dominant Osteopetrosis Type 2 (ADO2), has been granted Orphan Drug Designation by the U.S. FDA. In addition, due to the serious manifestations of this rare skeletal disorder in children, SIS-101-ADO has been granted Rare Pediatric Disease Designation for the treatment of Autosomal Dominant Osteopetrosis. FDA Orphan Drug Designation provides SiSaf with incentives such as tax credits for clinical trials, exemption from user fees, and expanded marketplace exclusivity. The Rare Pediatric Disease Designation entitles SiSaf to apply for a priority review voucher that can be used to have the drug approval process expedited by the FDA. The FDA awarded SIS-101-ADO Rare Pediatric Disease Designation on the basis of the serious or life-threatening manifestations of ADO that primarily affect children including blindness from optic nerve compression, anomalies in dental and craniofacial development, and scoliosis. There are currently no approved treatments for Osteopetrosis ADO2 and no other treatments currently in clinical trials. If approved, SiSaf’s SIS-101-ADO would thus be the first treatment for Osteopetrosis ADO2 and could provide life-altering benefits for those who suffer from this debilitating disease. SiSaf is currently preparing for first-in-human clinical trials. SIS-101-ADO combines an siRNA that suppresses the expression of CLCN7 with SiSaf’s Bio-Courier delivery technology. By downregulating the expression of CLCN7, a mutant gene expressed by osteoclasts and other cell types responsible for causing ADO2, the RNA therapy restores bone mass and quality to nearly normal levels. Genetic skeletal disorders such as ADO2 account for five percent of all birth defects globally, yet many unmet needs and challenges remain for providing safe and effective treatments. SiSaf’s proprietary Bio-Courier technology has the potential to accelerate the development of new RNA-based treatments. The technology addresses the limitations of other RNA delivery technologies by stabilizing lipid nanoparticles with bioabsorbable silicon. SiSaf’s Founder and CEO, Dr. Suzanne Saffie-Siebert, said, “Being granted Orphan Drug Designation and Rare Pediatric Disease Designation is a major milestone in our drive to move our revolutionary siRNA treatment forward to alleviate the pain and suffering that Osteopetrosis ADO2 inflicts. SIS-101-ADO ushers in the potential for a new era of personalized care and treatment options for ADO2 and other rare bone and skeletal diseases.” There has been an explosion of interest in RNA therapeutics for a wide range of medical conditions and SiSaf’s innovative Bio-Courier delivered siRNA technology holds the promise to address some of the most intractable diseases. "SIS-101-ADO and other Bio-Courier formulated drugs will not only be able to treat rare skeletal disorders but can clear the way for therapeutics for other rare diseases once thought impossible to treat,” added Dr Saffie-Siebert. Bio-Courier Technology Program and its Benefits SiSaf’s Bio-Courier drug delivery platform builds upon lipid nanoparticle technology with the introduction of silicon, for structural integrity and durability. The result is a nanoparticle with improved RNA loading capacity and protection from hydrolysis, combined with efficient transfection and controlled release of the oligonucleotide payload. Bio-Courier versatility is achieved by modifying particle size, surface charge and surface ligands for targeting to the desired site of drug action. Bio-Courier formulated drugs can be used for multiple routes of administration. About Orphan Drug Designation Orphan Drug Designation is a process designated by the FDA for therapeutics that have promising, but limited, efficacy in the marketplace. The FDA has authority to grant Orphan Drug Designation to a drug or biological product to prevent, diagnose or treat a rare disease or condition – typically affecting 200,000 people or less – through incentives such as tax credits for clinical trials, exemption from user fees, and expanded marketplace exclusivity. About Rare Pediatric Disease Designation Under Section 529 to the Federal Food, Drug, and Cosmetic Act (FD&C Act) the FDA will award priority review vouchers to sponsors of rare pediatric disease product applications that meet certain criteria. Under this program, a sponsor who receives an approval for a drug or biologic for a "rare pediatric disease" may qualify for a priority review voucher that can be redeemed to receive a priority review of a subsequent marketing application, including applications for a different product. SiSaf is working with CSSi LifeSciences, a leader in shepherding emerging therapeutics through federal approval processes, to co-ordinate the complex regulatory process that is required for the clinical trials of SIS-101-ADO. About SiSaf SiSaf is an RNA delivery and therapeutics company. Its proprietary Bio-Courier technology addresses the limitations of other RNA delivery technologies through the hybridization of organic materials with inorganic, bioabsorbable silicon. Led by founder and leading biomaterials specialist Dr. Suzanne Saffie-Siebert, SiSaf is a private company supported by venture capital investors including Vickers Venture Partners and the UK Future Fund. 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 about SiSaf and this program, submit this contact form or visit: Media Contacts Scius Communications Sue Charles – sue@sciuscommunications.com +44 7968 726585 Daniel Gooch – daniel@sciuscommunications.com +44 7747 875 479