IONIS PHARMACEUTICALS INC (IONS)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 revenue was $227M, up sequentially vs. Q3 ($134M) but down year over year vs. Q4 2023 ($325M); GAAP diluted EPS was $(0.66) vs. $(0.95) in Q3 and $(0.06) in Q4 2023 .
• Management framed the quarter as the start of Ionis’ “fully integrated commercial-stage” chapter, with its first independent launch (TRYNGOLZA for FCS) and accelerating WAINUA royalties; FY24 revenue totaled $705M and non-GAAP operating loss was $345M, both better than guidance according to management’s commentary .
• 2025 guidance introduced: revenue >$600M, non-GAAP operating loss <$(495)M, year-end cash ≈$1.7B, reflecting a shift toward commercial revenue from TRYNGOLZA and potential donidalorsen product revenue post-approval .
• Near-term catalysts: donidalorsen PDUFA (Aug 21, 2025), sHTG Phase 3 (CORE/CORE2) data in H2:2025, and continued global rollout of WAINUA; management highlighted multiyear launch cadence and a path to positive cash flow .

What Went Well and What Went Wrong

What Went Well

• “Ionis has begun a new chapter as a fully integrated commercial-stage biotechnology company” with the first independent launch of TRYNGOLZA; first prescription within 24 hours, drug in channel within 1 week, first patient on therapy in 2 weeks .
• WAINUA royalties accelerated with Q4 royalties of $10M and strong Q4 product demand (product sales +84% vs. Q3), supporting sequential revenue growth and broader adoption across centers of excellence and community settings .
• FY24 revenue and non-GAAP operating loss exceeded guidance; management raised confidence in a multiyear launch plan and highlighted a clear path toward sustained positive cash flow .

What Went Wrong

• Year-over-year revenue declined in Q4 (to $227M from $325M), driven by lower R&D revenue (notably a reduction in WAINUA joint development revenue as ATTRv-PN development wound down post-launch) .
• GAAP net loss remained significant in Q4 at $(104)M, reflecting ongoing commercial build-out (SG&A up for launch activities) and R&D investment; operating loss was $(110)M .
• Consensus estimates were unavailable at time of analysis due to S&P Global API limits, preventing a formal beat/miss assessment for revenue/EPS versus Street expectations (S&P Global consensus unavailable).

Financial Results

Revenue, EPS, Operating Results (chronological: oldest → newest)

Margins (derived from reported results; citations reference source figures)

Segment/Revenue Breakdown

KPIs and Operating Metrics

Notes: Non-GAAP excludes equity-based compensation and related tax effects per company reconciliation .

Guidance Changes

Management indicated 2025 revenue mix shifting toward commercial, reflecting TRYNGOLZA and anticipated donidalorsen post-approval .

Earnings Call Themes & Trends

Management Commentary

• CEO: “Ionis has begun a new chapter as a fully integrated commercial stage biotechnology company with our first independent launch of TRYNGOLZA underway,” highlighting a multiyear cadence of independent and partnered launches and a path to positive cash flow .
• CGPSO: “Following approval of TRYNGOLZA, the first prescription was written within 24 hours… first patient self-administered within 2 weeks… breadth of prescribers and rapid time from prescription to patients receiving TRYNGOLZA” .
• CFO: “We delivered a non-GAAP operating loss of $345M… substantially exceeded our 2024 revenue guidance by more than $130M, earning revenues of $705M… project to earn more than $600M in revenue [in 2025]… non-GAAP operating loss of less than $495M… end the year with cash… ≈$1.7B” .

Q&A Highlights

• sHTG read-through: ESSENCE will primarily inform safety/target engagement; CORE/CORE2 powered on triglyceride lowering; AP reduction signal plausible given FCS BALANCE data, though not powered on AP in sHTG .
• WAINUA uptake: Q4 product sales nearly doubled vs. Q3; ~40% new-to-brand share; strong reimbursement with most patients paying $0 out-of-pocket .
• TRYNGOLZA reimbursement: Genetic confirmation is the most straightforward; clinical diagnosis acceptable through medical exception with documented history; rapid genetic diagnosis (1–2 weeks) observed .
• Commercial scaling: VP of Sales for donidalorsen hired; sequential build of field teams ahead of PDUFA; sHTG commercialization to expand substantially given larger patient population .
• Ex-U.S. strategy: Plan to secure OUS partners for TRYNGOLZA (FCS and sHTG) and maintain focus on U.S. for near-term launches .

Estimates Context

• Wall Street consensus (S&P Global) for Q4 2024 revenue and EPS was unavailable at the time of request due to API limits, so formal beat/miss versus Street could not be assessed (S&P Global consensus unavailable).
• Given sequential Q4 revenue improvement and improved EPS versus Q3, estimates may need to reflect faster-than-expected WAINUA royalty ramp and early TRYNGOLZA contributions, but the absence of consensus precludes precise quantification .

Key Takeaways for Investors

• Sequential momentum: Q4 revenue recovered to $227M (from $134M in Q3), led by stronger commercial contributions (SPINRAZA and WAINUA royalties), even as R&D revenue declined YoY with ATTRv-PN development winding down .
• Launch execution: Early TRYNGOLZA execution is strong, with rapid patient onboarding and positive payer access; expect a gradual ramp given rare, underdiagnosed FCS, with momentum building through 2025 .
• 2025 setup: Guidance implies increasing commercial mix and back-half weighting from milestones and potential donidalorsen product sales post-approval; year-end cash ≈$1.7B provides ample runway .
• Pipeline catalysts: CORE/CORE2 sHTG data in H2:2025 could unlock a broader olezarsen indication; donidalorsen PDUFA on Aug 21; WAINUA growth across geographies supports royalty durability .
• Operating leverage: Non-GAAP operating loss guidance (<$495M) reflects disciplined expense growth amid commercial scaling; continued focus on driving leverage with multiyear launch cadence .
• Trading lens: Watch regulatory/timeline updates (doni PDUFA, sHTG readouts), WAINUA royalty trajectory, and early TRYNGOLZA metrics; stock likely sensitive to sHTG efficacy/safety profile and payer dynamics in FCS .
• Risk checks: R&D revenue timing variability (milestones/back-half weighting) and conversion dynamics in donidalorsen’s “switch” market could introduce ramp timing variability .