Silence Therapeutics plc

We are a biotechnology company focused on discovering and developing new molecules that use short interfering ribonucleic acid (siRNA) to stop specific target genes from expressing. These genes are believed to contribute to diseases with significant unmet medical needs. Our siRNA molecules are designed to utilize the body's natural RNA interference (RNAi) mechanism by specifically attaching to and breaking down messenger RNA (mRNA) molecules that code for particular disease-associated proteins within a cell. By degrading the mRNA that codes for a disease-associated protein, the production of that protein is reduced, and its activity level is lowered. This reduction in disease-associated protein production and activity is known as "gene silencing" in RNAi therapeutics. Our proprietary mRNAi GOLD™ (GalNAc Oligonucleotide Discovery) platform creates siRNA product candidates designed to precisely target and 'silence' specific disease-associated genes in the liver. Through this platform, we have developed siRNA product candidates for rare and common diseases where current treatments are limited or insufficient. For rare diseases, Divesiran (SLN124) is our potential first-in-class siRNA in Phase 2 development for polycythemia vera (PV). PV is a rare myeloproliferative neoplasm characterized by an overproduction of red blood cells (RBCs). A key indicator of PV is elevated hematocrit (HCT), which is an index of RBC mass. HCT levels above 45% increase the risk of thrombotic and cardiovascular events. Divesiran works by "silencing" the TMPRSS6 gene, which removes the natural inhibition on hepcidin, the body's main iron regulator. When TMPRSS6 is reduced in individuals with PV, hepcidin levels increase, decreasing iron availability to the bone marrow. With less iron available, the excessive production of RBCs seen in PV is reduced. This helps maintain HCT levels within a safer range and can lessen or eliminate the need for phlebotomies. Additionally, siRNA therapies offer a highly potent and lasting effect, allowing for less frequent and more convenient dosing.