Summary of Silence Therapeutics Conference Call Company Overview - Silence Therapeutics is a global clinical stage biopharmaceutical company with a proprietary small interfering RNA (siRNA) technology platform known as GOLD (GalNAc Oligonucleotide Discovery platform) targeting liver diseases [3][4] Technology and Programs - The company utilizes GalNAc-directed ligands to effectively target hepatocytes, focusing on conditions where disease-associated proteins are produced in the liver [3] - Silence has a robust intellectual property library and is continuously optimizing its technology [4] Current Clinical Programs 1. **SLN360 (Targeting Lp(a))** - Phase three ready but awaiting partnership for cardiovascular outcome trial [5][6] - Lp(a) is a genetically defined cardiovascular risk factor, not modifiable by diet or exercise [6] - The company has received positive feedback from regulatory agencies (FDA, EMA, PMDA) [5] 2. **SLN124 (Targeting Polycythemia Vera)** - Currently in phase two, targeting TMPRSS6 to manage overproduction of red blood cells [7][9] - The mechanism of action involves increasing hepcidin to restrict iron availability to bone marrow, reducing RBC production [9][10] - The market for polycythemia vera is estimated at 150,000 patients in the US and approximately 3.5 million worldwide [14] 3. **AstraZeneca Partnership** - Collaboration allows for the advancement of up to 10 potential programs, with the first in phase one [42] Phase One Data Highlights for SLN124 - The phase one study included 21 patients, with half maintaining hematocrit below 45% without the need for phlebotomy [17][18] - Significant reductions in hematocrit levels were observed, with improvements in iron status indicated by elevated ferritin levels [19][20] - The phase two trial is set to confirm the Q6 week dosing strategy and explore quarterly dosing [21][24] Competitive Landscape - Silence Therapeutics differentiates its Lp(a) program by targeting a broader population of high-risk patients and potentially lowering entry criteria for trials [35][36] - The company aims to demonstrate robust and durable effects with less frequent dosing compared to competitors [30][34] Upcoming Milestones - Completion of the phase two trial for SLN124 is expected in the early third quarter of 2026 [25] - Anticipated key events in the Lp(a) space include Novartis and Amgen trials demonstrating cardiovascular outcomes related to Lp(a) lowering [43][44] - Silence is also exploring preclinical opportunities and targeting extrahepatic conditions with its siRNA technology [44][45] Financial Position - As of September 30, Silence Therapeutics reported approximately $102 million in cash, sufficient to support operations until 2028 [47]