SLN

• Zerlasiran: ALPACAR-360 Phase 2 study showed Lp(a) reductions >90%, well tolerated. Phase 3 program design highly differentiated, met with positive regulatory feedback. Phase 3 outcomes study will be initiated only once a partner is secured.
• Divesiran: SANRECO Phase 1 study showed complete elimination of phlebotomy need in well-controlled patients, safety/tolerability favorable. Started SANRECO Phase 2 study, EU granted Orphan Drug Designation for PV, FDA Fast Track and Orphan Drug Designations also obtained.
• Pipeline advancements: Third siRNA from GOLD platform entered clinic under AstraZeneca collaboration. Progressed preclinical siRNA candidates for hepatic targets. Plan to start Phase 1 study of SLN548 in second half of 2025.
• 2025 priorities: Prioritizing investment in programs targeting rare conditions with first-in-class/best-in-class siRNAs. Focus on divesiran for PV, and advancing other pipeline programs including extrahepatic work.

• Will only initiate zerlasiran Phase 3 outcomes study once a partner is secured, extending cash runway into 2027.
• Prioritizing programs targeting rare conditions with clear unmet needs for innovative siRNA therapies, including divesiran for PV.
• Anticipate full enrollment in SANRECO Phase 2 study by end of 2024. Plan to start Phase 1 study of SLN548 in second half of 2025.

For the year ended December 31, 2024, Silence recorded $43.3 million in revenues versus $31.6 million in 2023. The increase was largely due to collaboration arrangements. Revenue from the AstraZeneca collaboration advanced nicely, and from the Hansoh Pharma collaboration, $24.6 million was recognized in 2024 due to cumulative catch-up. Expenses: R&D costs were $67.9 million in 2024 vs $56.9 million in 2023, primarily due to advancing zerlasiran and divesiran programs. General and administrative costs were $26.9 million in 2024 vs $26.2 million in 2023, driven by transition to U.S. domestic issuer requirements. Net operating loss in 2024 was approximately $63.3 million vs $64.4 million in 2023, with net loss at $45.3 million vs $54.2 million in 2023. Cash, cash equivalents, and short-term investments were $147.3 million at year-end 2024.

Actual results may differ materially from forward-looking statements due to various factors including those in the most recent annual report on file with the SEC and future filings. No specific operational failures discussed in detail.

Q: Provide color on partnership discussions for zerlasiran and importance of HORIZON data, types of partnership structures considered?

A: Not to comment specifically on ongoing discussions, but actively engaged in partnering, confident in zerlasiran's potential, balance resources among products.

Q: How ready are you for Phase 3 trial of zerlasiran, timeline from securing partner, partner influence on Phase 3 design, evaluation of divesiran in hereditary hemochromatosis?

A: Phase 3 readiness activities on track to complete by mid-year. Can make fine-tuning with partner. Considering divesiran in hereditary hemochromatosis as it relates to the target.

Q: Goal for divesiran differentiation, differentiation vs rusfertide besides dosing frequency, biggest hurdles in partnering zerlasiran?

A: Goal is to be first siRNA to market for PV, differentiation includes dosing frequency and symptomatic improvement. No single hurdle for partnering, dialogues around business strategy and market opportunity.

Q: Status of candidates developed for Hansoh, worth pursuing on own?

A: Interested in programs, have encouraging preclinical data, can develop ourselves or partner/license. Revenue from Hansoh is from cumulative catch-up, no further obligations.

Q: Regulatory discussions on zerlasiran dose, difference between endogenous trigger with TMPRSS6 inhibition and hepcidin mimetic in PV safety?

A: Not sharing specific dose info with regulators yet. Our approach of increasing hepcidin within physiological range is safe, correlation with clinical benefit seen in Phase 1, safety profile favorable