Amylyx Pharmaceuticals, Inc. (AMLX)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 reflected the transition to a pipeline-driven story: net product revenue was $(0.67)M and diluted EPS was $(0.55), driven by the April 2024 discontinuation of RELYVRIO/ALBRIOZA and associated returns/commitments; management emphasized strong cash runway through end of 2026 after raising $65.5M in Jan-2025 .
• Execution milestones strengthened: pivotal Phase 3 LUCIDITY for avexitide (PBH) recruiting began in Feb-2025, with dosing expected in Mar/Apr, completion of enrollment in 2025 and topline in H1 2026; Phase 2b ORION (PSP) fully enrolled (139 participants) with interim unblinded analysis in Q3 2025; Phase 1 LUMINA (ALS) recruiting with early cohort data expected in 2025 .
• Week 48 HE LIOS (Wolfram) data expected “in the coming months,” following positive topline (Week 24, sustained at Weeks 36/48) presented in Oct-2024, supporting Phase 3 planning .
• Estimates comparison: Wall Street consensus (S&P Global) was unavailable; note estimates may need to reset to near-zero revenue until commercialization resumes (avexitide earliest launch targeted 2027 if approved) .
• Potential stock catalysts near term: LUCIDITY enrollment progress and site activation updates, Week 48 Wolfram data, ORION interim in Q3 2025, and U.S. site expansion for AMX0114 .

What Went Well and What Went Wrong

What Went Well

• “We made significant progress in 2024 across our pipeline…we advanced our lead investigational asset avexitide into a pivotal Phase 3 trial and expect topline results in the first half of 2026” — Co-CEOs Joshua Cohen & Justin Klee .
• LUCIDITY initiated with FDA-agreed primary outcome; consistent prior PBH data showed 53% reduction in Level 2 and 66% reduction in Level 3 events at 90 mg QD; management confident in design and powering .
• Financing extended cash runway through end of 2026; commercial preparations underway with appointment of CCO Dan Monahan (ex-Otsuka, Novartis, Sanofi) .

What Went Wrong

• Revenue essentially nil/negative due to product withdrawals and accrual adjustments; Q4 net product revenue $(0.67)M and net loss $(37.55)M; legacy cash outflows of $31.0M in Q4 for returns/rebates and purchase commitments; residual obligations $7.8M remain .
• Year-over-year comparison stark: Q4 2023 revenue $108.45M and diluted EPS $0.07 vs Q4 2024 revenue $(0.67)M and diluted EPS $(0.55) .
• U.S. FDA constraints previously created timing friction for AMX0114; while recruiting has begun in Canada and U.S. sites are being opened, the path required additional regulatory interactions (Q3 context: clinical hold at FDA at lower starting dose) .

Financial Results

Quarterly Comparison (Q2 → Q3 → Q4 2024)

Notes: Q4 operating cash used ~$27M, plus ~$31M to settle returns/rebates and prior purchase commitments tied to discontinuation; residual obligations $7.8M expected to be paid through 2025 .

Year-over-Year (Q4 2023 vs Q4 2024)

KPIs and Balance Sheet

Segment breakdown: Not applicable (no active commercial segments reported in quarter) .
Non-GAAP/one-time items context: 2024 included inventory impairment and loss on firm purchase commitments ($118.68M FY) and restructuring charges ($22.85M FY), though Q4 quarterly lines did not show new inventory impairment; Q4 cash uses included $31.0M for returns/rebates and purchase commitments .

Guidance Changes

No numerical revenue, margin, OpEx, OI&E, tax rate, or dividend guidance provided in Q4 materials .

Earnings Call Themes & Trends

Management Commentary

• “We are entering a pivotal stage…key milestones across 3 assets in 4 ongoing clinical trials” — Co-CEO Justin Klee .
• “We ended 2024 in a solid cash position of $176.5 million…expect our cash runway to take us through 2026” — CFO James Frates .
• “Avexitide…90 mg once daily…statistically significant reduction in hypoglycemic events: 53% (Level 2) and 66% (Level 3)” — CMO Camille Bedrosian .
• “With a proven commercial and medical team in place, we believe we are well positioned for a potential first-to-market launch of avexitide in PBH” — Co-CEO Joshua Cohen .

Q&A Highlights

• PBH trial criteria and market scope: Limiting to Roux-en-Y to reduce heterogeneity; PBH estimated ~160,000 in U.S.; intention for broader PBH indication post-approval .
• GLP-1 antagonist vs agonists: Avexitide is a GLP-1 antagonist; distinct from weight-loss agonists; potential broader application in hyperinsulinemic hypoglycemia; investing in long-acting antagonist with Gubra .
• Market trajectory: Despite GLP-1 use, bariatric surgery demand persists; PBH is chronic; market expected to grow over time .
• PSP endpoints/analysis: Consistency between PSPRS 10-item vs 28-item; interim assessment to evaluate clinical activity vs placebo on PSPRS with biomarker context (tau) .
• Safety/pharmacology: Avexitide designed to restore homeostasis rather than induce hyperglycemia; favorable tolerability profile; 90 mg QD maintains therapeutic exposure ~24 hours .

Estimates Context

• Wall Street consensus estimates (S&P Global) for Q4 2024 and prior quarters were unavailable at time of review due to data access limits. As such, explicit “vs. estimates” comparisons cannot be provided. Given near-zero/negative reported revenue post-April 2024 discontinuation, estimates likely need to reflect minimal revenue until avexitide commercialization (targeted 2027 if approved) .

Key Takeaways for Investors

• Near-term thesis is execution-driven: LUCIDITY enrollment and site activation updates, Week 48 Wolfram data, and Q3 2025 PSP interim will shape the probability-weighted value of AMLX .
• Balance sheet adequate through end of 2026 after $65.5M raise; Q4 cash outflows from legacy obligations largely recognized, with $7.8M remaining in 2025; monitor quarterly burn and milestone cadence .
• Avexitide’s prior PBH data are compelling; pivotal design aligned with FDA guidance and prior trials — strong positioning for first approved therapy in PBH if Phase 3 is successful .
• AMX0035 programs: Wolfram signal across multiple measures and sustained over time bolsters Phase 3 planning; PSP interim (tau biology + PSPRS endpoint) is a key proof point .
• AMX0114 (ALS) is earlier stage but strategically important; watch for U.S. site activation progress and early cohort readouts in 2025 .
• Trading implications: Stock likely sensitive to LUCIDITY recruitment pace, Wolfram Week 48 data quality, and PSP interim signal; limited top-line revenue reduces downside from misses on commercial metrics but elevates binary clinical risk .
• Medium-term: If avexitide succeeds, PBH orphan market (estimated ~160,000 in U.S.) and first-to-market status could reset valuation; commercial build (CCO hire) underway to support potential 2027 launch .

Appendix: Additional Data Points

• Q4 R&D $22.9M and SG&A $17.1M; total operating expenses down materially YoY reflecting restructuring and commercialization wind-down .
• FY 2024 included inventory impairment and loss on firm purchase commitments of $118.68M and restructuring expense of $22.85M; underscores the transition year profile .
• Corporate collaborations: Gubra (long-acting GLP-1 antagonist) to identify lead candidate for IND-enabling studies .