Executive Summary

Q4 2024 was defined by a negative clinical event: izokibep failed to meet the primary endpoint in non‑infectious, non‑anterior uveitis, prompting management to cease further internal investment in the program .
Lonigutamab remained the core focus: ACELYRIN completed a positive end‑of‑Phase‑2 interaction with FDA in Q4 and detailed a Phase 3 LONGITUDE program design shortly after the quarter (100 mg loading, then 50 mg Q2W; ~350 patients across two global trials; proptosis response at 24 weeks) .
FY 2024 net loss was $248.2M on total operating expenses of $316.3M; year‑end liquidity (cash, cash equivalents, restricted cash, and marketable securities) was $448.4M, with runway projected to mid‑2027 including lonigutamab Phase 3 and BLA‑enabling activities .
Near‑term catalysts into 1H25/2H26: LONGITUDE Phase 3 initiation (Q1 2025) and topline Phase 3 readout in 2H 2026 (tone remained confident on enrollment and design) .

What Went Well and What Went Wrong

What Went Well

Positive FDA interaction on lonigutamab: “completed a positive end of Phase 2 (EOP2) interaction…alignment on important elements of the Phase 3 registrational program” .
Strengthened development plan: Phase 3 LONGITUDE program (100 mg load → 50 mg Q2W; active and chronic patients; 24‑week proptosis primary endpoint; dosing through 52 weeks) rolled out, supporting potential differentiation and chronic dosing strategy .
Financial discipline and runway: FY year‑end liquidity was $448.4M, with runway projected to mid‑2027, covering lonigutamab Phase 3/BLA‑enabling work and selective pipeline expansion .

What Went Wrong

Izokibep uveitis: Trial failed primary endpoint (treatment failure rate 45.0% vs 50.7% placebo at 24 weeks; no secondary endpoints met), leading to discontinuation of internal development; management noted disappointment and swift focus on lonigutamab .
Elevated operating burn in FY 2024: Total operating expenses of $316.3M and net cash used in operations of $303.9M reflected multi‑program activity (izokibep trials and CMC) and restructuring charges; $31.0M license payment to Pierre Fabre also hit R&D in FY 2024 .
Restructuring required to refocus pipeline: Charges of $11.4M in FY 2024 (severance and CMC cancellations net of credits) and workforce reduction to align spend with lonigutamab priorities .

Financial Results

ACELYRIN is a clinical‑stage company with no product revenue. The company did not publish a standalone Q4 2024 earnings press release; results are presented in the FY 2024 10‑K. Q4‑specific metrics were not disclosed; below are annual metrics and recent quarterly benchmarks.

Annual results (FY 2023 vs FY 2024)

Metric	FY 2023	FY 2024
Total Operating Expenses ($USD Millions)	$422.1	$316.3
Net Loss ($USD Millions)	$(381.6)	$(248.2)
Cash, Cash Equivalents, Restricted Cash + Short‑term Marketable Securities ($USD Millions)	$721.3 (Cash & equivalents $218.1 + marketable $503.2; no restricted cash disclosed)	$448.4

Recent quarterly benchmarks (Q2 vs Q3 2024)

Metric	Q2 2024	Q3 2024
R&D Expense ($USD Millions)	$76.4	$31.6
G&A Expense ($USD Millions)	$16.6	$12.3
Net Loss ($USD Millions)	N/A	$(48.5)
Cash at Period End ($USD Millions)	~$635.0 (end Q2 cash)	$562.4 (cash, cash equivalents, and short‑term marketable securities)

Note: Q4 2024 quarter metrics (revenue/EPS/margins) were not disclosed in a standalone Q4 press release; only FY data were provided in the 10‑K .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Year‑end Cash (2024)	FY 2024	$420–$450M (Q2 guidance)	$435–$450M (Q3 update)	Raised midpoint
Cash Runway	Through mid‑2027	To mid‑2027 (Q2)	To mid‑2027 (Q3/FY reaffirmed)	Maintained
Lonigutamab Phase 3	Initiation	Q1 2025 planned (Q3)	Q1 2025 expected; topline 2H 2026	Timelines specified

Earnings Call Themes & Trends

Topic	Previous Mentions (Q-2 and Q-1)	Current Period (Q4 2024)	Trend
Lonigutamab dosing strategy & Phase 3 design	Added 70 mg cohort every 3–4 weeks; moving directly to Phase 3 with potential concurrent trials	Positive FDA EOP2; Phase 3 LONGITUDE design announced (100 mg LD → 50 mg Q2W; active/chronic; 24‑week proptosis; 52‑week dosing)	Advancing per plan
Uveitis (izokibep) program	Trial design akin to HUMIRA VISUAL; results expected in Dec. 2024	Topline fail; no primary/secondary significance; discontinuation of internal development	Negative; program stopped
Financial discipline & runway	Q2 guided YE cash $420–$450M; runway to mid‑2027	Q3 updated YE cash to $435–$450M; FY liquidity $448.4M; runway reaffirmed	Maintained

Management Commentary

Strategic focus: “We are executing on our refocused pipeline strategy…advance subcutaneous lonigutamab into Phase 3” .
On uveitis outcome: “We are very grateful… and, like them, we are disappointed that it did not meet its primary endpoint…we will not make any additional internal investment in developing izokibep” .
Phase 3 design intent: “evaluate…100mg loading dose…followed by 50mg dose every two weeks…primary endpoint in both trials will be proptosis response rate at 24 weeks…dose out to 52 weeks” .
Pipeline & cash: “projected to provide cash runway to mid‑2027…including completion of planned Phase 3 trials and BLA‑enabling activities for lonigutamab” .

Q&A Highlights

Dose selection & loading strategy: Emphasis on establishing a narrow therapeutic window (sufficient Cmin, mitigated Cmax) for efficacy with improved safety; cohort work supports confidence entering Phase 3 .
Hearing safety: No audiogram‑measured hearing impairment reported across dose cohorts to date; transient tinnitus cases in Cohort 1 resolved without audiogram changes .
Uveitis pathway: If data were positive, one additional ~200–250 patient Phase 3 would be anticipated for registration; actual results were negative and program stopped .
Financial guidance & manufacturing: Manufacturing commitments for izokibep were resolved via payment and credit voucher; YE cash raised to $435–$450M .

Estimates Context

Wall Street consensus estimates (S&P Global) for SLRN were unavailable due to missing CIQ mapping; comparisons to consensus could not be made. Values retrieved from S&P Global were unavailable.

Key Takeaways for Investors

The uveitis miss removes an ancillary asset and sharpens focus on lonigutamab; near‑term value is tied to Phase 3 execution and potential differentiation (subcutaneous dosing, chronic treatment durability) .
Regulatory and design de‑risking: Positive EOP2 and detailed Phase 3 protocol lower execution risk; topline timing (2H 2026) provides clear catalyst path .
Balance sheet supports the pivotal plan: $448.4M in liquidity and runway to mid‑2027 should fund lonigutamab through Phase 3 and BLA‑enabling activities without assumed partnerships .
Operating discipline remains essential: FY operating expenses ($316.3M) and cash use ($303.9M) reflect the transition from multi‑program activity to a lonigutamab‑focused plan; restructuring and CMC credits help moderate forward burn .
Safety/PK positioning: Early data suggest efficacy at lower exposures vs IV anti‑IGF‑1R agents and no audiogram‑measured hearing impairment to date—key for payer and physician adoption if efficacy is confirmed .
Near‑term watch‑items: Phase 3 trial initiation details and enrollment pace in Q1 2025; any updates on manufacturing scale‑up and chronic dosing outcomes; investor day depth on differentiation .

Supporting Documents Read

FY 2024 10‑K (financials, liquidity, pipeline and restructuring) .
Q3 2024 earnings press release (cash, expenses, runway, pipeline milestones) .
Q3 2024 earnings call transcript (strategic commentary, Q&A) .
Q2 2024 earnings call transcript (lonigutamab Phase 2/3 strategy, expenses, YE cash guidance) .
Dec 10, 2024 press release—izokibep uveitis topline failure .
Jan 6, 2025 8‑K—lonigutamab Phase 3 LONGITUDE program design .

ACELYRIN, Inc. (SLRN)·Q4 2024 Earnings Summary