Peer-Reviewed Publication of Positive Preclinical Data of SiSaf’s SIS-ADO2 siRNA Program to Treat Rare Genetic Bone Disorder Osteopetrosis

Data published in the Cell Press Journal Molecular Therapy Nucleic Acids

Guildford, England, 18 September – 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.