Silence Therapeutics plc (SLN)·Q4 2024 Earnings Summary

Executive Summary

• Silence Therapeutics reported FY 2024 financials alongside its Q4 2024 update and extended cash runway guidance into 2027 after deciding to initiate zerlasiran’s Phase 3 CV outcomes trial only with a partner in place, prioritizing divesiran in PV and rare disease programs .
• FY 2024 collaboration revenue rose to $43.3M, net loss narrowed to $45.3M, and year-end liquidity reached $147.3M (cash, cash equivalents, and short-term investments), underpinning the runway extension and program prioritization .
• Clinical execution remained strong: zerlasiran Phase 2 ALPACAR-360 showed >80% mean time-averaged Lp(a) reduction with durability and good tolerability; divesiran Phase 1 in PV reduced phlebotomy frequency and lowered hematocrit with favorable safety, with Phase 2 enrollment underway and full enrollment anticipated by YE 2025 .
• Key catalyst and stock narrative driver: partnership timing/terms for zerlasiran Phase 3 and continued PV data flow; management emphasized active partnering dialogue and cash discipline while maintaining confidence in zerlasiran’s competitive profile .

What Went Well and What Went Wrong

What Went Well

• Divesiran Phase 1 in PV demonstrated elimination of phlebotomy in well-controlled patients, reductions in hematocrit across cohorts, physiologic hepcidin increases, and favorable safety; Phase 2 dosing initiated and enrollment expected to complete in 2025 (“we anticipate full enrollment … by the end of this year”) .
• Zerlasiran Phase 2 ALPACAR-360 produced >80% mean time-averaged Lp(a) reductions over 36 weeks, >90% maximum reductions, with effects persisting at 60 weeks and good tolerability (“no safety concerns emerged with infrequent dosing”) .
• FY 2024 revenue growth and narrowed net loss versus FY 2023, supported by cumulative catch-up under collaborations and disciplined cash management; year-end cash and short-term investments of $147.3M .

What Went Wrong

• Decision to defer zerlasiran Phase 3 initiation until a partner is secured delays the program timeline versus earlier expectations; Phase 3 start now explicitly “dependent on partnership” .
• Quarterly collaboration revenue variability persisted; Q3 2024 revenue declined to £1.1M from £2.8M YoY with cost of sales exceeding revenue in the quarter (timing of milestones and project progression) .
• Hansoh opted not to pursue further development under the collaboration, eliminating expected future Hansoh revenue streams; SLN retains rights and is evaluating next steps .

Financial Results

Note: FY 2024 figures are reported under U.S. GAAP in USD; interim Q2/Q3 figures are IFRS in GBP.

Annual Results (USD, U.S. GAAP)

Liquidity and Balance (USD)

Quarterly Trend (GBP, IFRS)

Segment reporting: the company reports a single business segment focused on RNAi therapeutics; CODM determined one segment in Q2/Q3 2024 filings .

KPIs:

• Contract liabilities (deferred revenue): £60.5M at June 30, 2024 and £60.5M–£60.5M range trending to £60.5M; £60.5M at Sept 30, 2024 (current £2.5M; non-current £58.0M) .
• R&D tax credit benefit: £3.7M in H1 2024 and £6.9M in nine months ended Sept 30, 2024 .

Versus estimates: Wall Street consensus from S&P Global for Q4 2024 revenue/EPS was unavailable in our session; SLN did not provide quarterly U.S. GAAP Q4 breakdown in its 8-K. As a result, beat/miss versus consensus cannot be evaluated.

Estimates Comparison

• S&P Global consensus estimates for Q4 2024 EPS and revenue: unavailable due to data access limits and lack of company-reported quarterly breakdown in the 8-K; therefore, comparison to estimates is not provided .

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “We are prioritizing investment in programs targeting rare conditions … While we remain confident in our zerlasiran program for high Lp(a), we will only initiate the Phase 3 cardiovascular outcomes study once a partner is secured.” — Craig Tooman, CEO .
• “We ended the year with over $147 million in cash, cash equivalents and short-term investments… The decision not to initiate the zerlasiran Phase 3 outcomes study without a partner extends our projected cash runway into 2027.” — Rhonda Hellums, CFO .
• “Divesiran completely eliminated the need for phlebotomy in all well-controlled patients… The safety and tolerability profile continues to look very favorable.” — Craig Tooman (call) .
• “Given hepcidin increases within physiologic range … we see robust outcomes—a reduction in the need for phlebotomy and maintenance of hematocrit.” — Steven Romano, Chief R&D Officer .

Q&A Highlights

• Zerlasiran partnership: Management underscored active discussions; timing and structures vary by counterparty; Phase 3 initiation gated to partnership, with readiness on track by mid-2025 .
• Divesiran differentiation vs rusfertide: Emphasis on infrequent dosing and potential convenience; efficacy driven by endogenous hepcidin upregulation within physiologic ranges; safety profile favorable thus far .
• Potential indications expansion: TMPRSS6 inhibition may have broader relevance (e.g., hereditary hemochromatosis); exploration ongoing, though no specific trial declared .
• Hansoh collaboration status: Hansoh discontinued further development; SLN retains global rights to three programs and will decide on internal vs partnered advancement .

Estimates Context

• S&P Global consensus (revenue, EPS) for Q4 2024 was not available within this session, and the company furnished FY 2024 results without a standalone U.S. GAAP quarterly breakout in its 8-K; therefore, we cannot assess beat/miss versus Wall Street for Q4 2024 .
• Implication: Near-term estimate revisions likely tied to cash runway extension (lower Phase 3 near-term spend) and program reprioritization; Street models may push zerlasiran Phase 3 timelines while increasing PV program value weighting .

Key Takeaways for Investors

• Cash runway extended into 2027 reduces financing risk and supports pipeline focus on divesiran and rare disease programs while partnering zerlasiran for Phase 3—an attractive de-risking step for capital allocation discipline .
• Zerlasiran’s AHA/JAMA data strengthen durability and dose-interval selection for Phase 3; partnership outlook is central to the stock narrative in 2025 .
• Divesiran PV program is advancing with favorable Phase 1 efficacy/safety and Phase 2 enrollment underway, with full enrollment targeted by YE 2025—visible 2025 clinical catalysts .
• FY 2024 financials show improved revenue and narrowed net loss; liquidity of $147.3M at year-end underpins flexibility for selective extrahepatic initiatives (SLN548 Phase 1 start in 2H 2025) .
• Collaboration mix is evolving (Hansoh exit; AstraZeneca milestones); regained rights could create optionality for partnering/licensing or internal advancement .
• Watch for: zerlasiran partner announcement/timing, PV Phase 1/2 data disclosures at medical meetings, and clarity around U.S. GAAP quarterly reporting cadence post domestic issuer transition .

Other Relevant Q4 2024 Press Releases

• AHA Late-Breaking ALPACAR-360 results (Nov 18, 2024): >80% mean time-averaged Lp(a) reductions; durability at 60 weeks; published in JAMA; strong safety profile with infrequent dosing .
• ASH divesiran PV update (Dec 9, 2024): sustained HCT reduction, reduced phlebotomy frequency, favorable safety; first subject dosed in Phase 2; SLN reinforces commitment to prioritize divesiran .

Notes:

• Single operating segment disclosed in filings covers RNAi-based therapeutics development .
• The company transitioned to U.S. domestic issuer reporting effective Jan 1, 2025; FY 2024 furnished in USD (U.S. GAAP) in the 8-K .