Silence Therapeutics (SLN) Piper Sandler 36th Annual Healthcare Conference summary

Pipeline overview and strategic approach

• Operates a global, hybrid model with proprietary siRNA programs and partnerships, including AstraZeneca, to secure non-dilutive funding.

• Two lead proprietary siRNA programs are advancing in the clinic, with strong data and upcoming presentations at ASH.

• Portfolio approach guides funding allocation, with ongoing evaluation of asset prioritization and potential partnerships for large-scale trials.

• Maintains a cash balance of $172 million as of Q3, expected to fund operations into 2026, leveraging partnerships for additional resources.

Zerlasiran (Lp(a) siRNA program)

• Zerlasiran achieves over 90% maximum knockdown of Lp(a) in phase 1 and 2 studies, outperforming previous drug classes.

• Demonstrates durable effect with infrequent dosing, potentially quarterly or longer, and a competitive safety profile.

• Phase 2 ALPACAR-360 study showed 81–86% time-averaged Lp(a) reduction at 16–24 week intervals, with maximum suppression above 90%.

• Phase 3 trial will likely enroll 6,000–8,000 patients globally, focusing on a broader high-risk vascular population and lower Lp(a) thresholds.

• Trial design aims to differentiate through broader inclusion criteria and payer engagement, with learnings from competitor studies.

Divesiran (PV siRNA program)

• Phase 1 open-label trial in polycythemia vera (PV) showed near elimination of phlebotomy need in well-controlled patients.

• 19 patients in phase 1 saw phlebotomies drop from 79 to 6 over the follow-up period, with robust and persistent effect.

• Phase 2 trial for PV is starting in December, targeting up to 65 patients, with orphan and fast-track designations.

• siRNA approach offers potential advantages over monoclonal antibodies and ASOs, including durability and safety.

• SLN124, the molecule behind PV, may have broader hematological applications in the future.