Silence Therapeutics (SLN) investor relations material

Platform and technology overview

• siRNA technology platform offers high efficacy, safety, durability, and reversibility, with a robust intellectual property estate and global operations in Berlin, UK, and the US.

• mRNAi GOLD™ platform targets messenger RNA to silence disease-associated proteins, providing specificity and potency in clinical applications.

• The technology is endogenous and allows flexible dosing, with broad applicability across large and rare disease indications.

• Artificial intelligence and machine learning are integrated into discovery, sequence selection, off-target evaluation, and trial design.

Clinical program updates

• Divesiran for polycythemia vera (PV) shows strong efficacy in phase 1, reducing hematocrit and phlebotomy needs, with phase 2 enrolling well-controlled patients and aiming for full enrollment by year end.

• The mechanism involves blocking TEMPR6 to elevate hepcidin, restricting iron to the bone marrow and reducing red blood cell production.

• Phase 2 focuses on maintaining hematocrit control, reducing phlebotomies, and assessing symptom improvement, with data expected in the second half of next year.

• Zerlasiran for Lp(a) is phase 3 ready, showing over 90% reduction in Lp(a) in trials, with durable effects and quarterly or less frequent dosing; partnership sought for large-scale CVOT.

Partnerships and pipeline strategy

• Multi-target collaboration with AstraZeneca covers up to 10 targets in cardiovascular, metabolic, respiratory, and renal areas, with phase 1 programs advancing.

• Prioritization of extrahepatic targets is underway, with preclinical data supporting expansion beyond liver indications.

• Cash position of $114 million as of Q2 2023 provides runway into 2028, supporting ongoing and future programs.

• Strategic focus on right-sized programs, especially rare diseases like PV, to align with resource capabilities.