Amylyx Pharmaceuticals, Inc. (AMLX)·Q1 2025 Earnings Summary

Executive Summary

• Q1 2025 delivered a narrower loss and significant OpEx reduction as the company transitions post-RELYVRIO, with net loss of $35.9M (-$0.42 EPS) and cash/marketable securities of $204.1M; cash runway reiterated through YE’26 .
• EPS modestly beat consensus (actual -$0.42 vs -$0.48 consensus mean), driven by materially lower R&D and SG&A; revenue was effectively zero as expected following the 2024 discontinuation of RELYVRIO/ALBRIOZA .*
• Execution advanced across the pipeline: first participant dosed in Phase 3 LUCIDITY for avexitide (PBH) and in Phase 1 LUMINA for AMX0114 (ALS); ORION (PSP) Phase 2b data expected in Q3 2025 and HELIOS (Wolfram) Week 48 data in May .
• Stock catalysts ahead: LUCIDITY enrollment completion (2025), ORION 2b data (Q3 2025), HELIOS Week 48 dataset (May 2025), and LUMINA early cohort readout (2025), with commercial preparations underway for avexitide if approved (target launch 2027) .

What Went Well and What Went Wrong

• What Went Well

  • LUCIDITY (avexitide, PBH) initiation and first patient dosed; timeline intact (enrollment 2025, topline 1H26). “We continue to expect enrollment completion in 2025 and top line data in the first half of 2026.”
  • AMX0114 (ALS) Phase 1 LUMINA dosed first participant; early cohort data in 2025; U.S. clinical hold lifted in January 2025 .
  • Cost discipline: Total OpEx down ~82% YoY per CFO; R&D $22.1M vs $36.6M YoY; SG&A $15.7M vs $57.8M YoY, supporting the EPS beat and runway through 2026 .

• What Went Wrong

  • No product revenue post RELYVRIO/ALBRIOZA discontinuation; Q1 revenue “—” vs $88.6M in Q1’24, pressuring scale and margin optics .
  • Residual cash outflows tied to legacy ALS product: ~$6.0M cash used in Q1 for rebates/commitments; $3.1M obligations remain through 2025 .
  • Continued R&D dependency for value inflection; near-term results (ORION 2b) carry program risk and could influence strategy and valuation .

Financial Results

Headline metrics vs prior periods and estimates

Notes: Revenue/EPS consensus from S&P Global; asterisked values indicate S&P Global data. Values retrieved from S&P Global.*

Operating expenses and cost structure

Balance sheet and cash KPIs

Segment breakdown: Not applicable (no active commercial segments; post-ALS product discontinuation) .

KPIs: cash runway “through the end of 2026” reiterated; residual cash obligations tied to RELYVRIO/ALBRIOZA $3.1M expected to be paid through 2025 .

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “We continue to expect enrollment completion in 2025 and top line data in the first half of 2026.” – Co-CEOs on avexitide LUCIDITY .
• “Total operating expenses for the quarter were $37.8 million, down 82% from the same period in 2024.” – CFO .
• “We did not see a meaningful [placebo] difference between the run-in and the placebo” in PBH Phase 2; powering robust for Phase 3. – Management on placebo effect .
• “We ended the first quarter with a cash position of $204.1 million… cash runway through the end of 2026.” – CFO .
• On PSP efficacy bogey: “The study has about 80% power to detect a 30% effect on the PSP rating scale… decision will be driven by all the data.” – Co-CEO .

Q&A Highlights

• PBH market education and patient identification: Education needed across rare disease stakeholders; symptoms often manifest 1–3 years post-surgery; sizable treated-symptomatic pool beyond the 160k persistent PBH estimate .
• PSP trial expectations: 80% power for a 30% effect on PSPRS; clinical meaningfulness will be assessed holistically across endpoints .
• Access: No approved PBH therapies; management does not anticipate payer step therapy; focus on efficient access .
• Avexitide safety: Competitive GLP-1 receptor antagonism with favorable clinical and nonclinical safety to date; no signals of hyperglycemia/weight gain observed .
• Wolfram Phase 3 design: Week 48 HELIOS data to inform protocol; ongoing FDA dialogue, with details pending alignment .

Estimates Context

• EPS: Beat – actual -$0.42 vs consensus -$0.48 (3 estimates). Driver: large YoY reductions in R&D and SG&A following ALS product exit and restructuring .*
• Revenue: In line – $0 given discontinued product sales; consensus $0 (4 estimates). Management previously highlighted removal of RELYVRIO/ALBRIOZA from market in 2024 .*

Note: Asterisked values from S&P Global consensus. Values retrieved from S&P Global.*

Key Takeaways for Investors

• Execution risk shifting to data readouts: Near-term HELIOS (May), medium-term ORION 2b (Q3’25), and LUMINA early cohort (2025) are principal stock catalysts; LUCIDITY topline in 1H26 is the core medium-term value driver .
• Avexitide commercial setup progressing: First patient dosed; management is preparing for a potential 2027 launch with an emphasis on patient/provider education and payer access in an orphan market without approved therapies .
• Balance sheet adequate through YE’26: $204.1M cash and reiterated runway provide funding for key clinical milestones and pre-launch activities without immediate financing needs .
• Cost base reset largely complete: OpEx down materially YoY; expect operating losses to track program cadence and milestone spend rather than commercial infrastructure, supporting EPS vs expectations .
• PBH market sizing and demand: Management frames ~160k persistent PBH in U.S. within a broader post-bariatric hypoglycemia population; education can expand diagnosis and treatment funnel if avexitide is approved .
• PSP program watchpoints: Powering and endpoints clarified; management to take a go/no-go based on totality of ORION Phase 2b data, making Q3’25 a pivotal decision point .
• ALS program offers optionality: Biomarker strategy (NfL) and mechanism (calpain-2) with early cohort data in 2025 could de-risk the asset and provide upside optionality .

Citations

• Q1 2025 8-K/Press release (financials, balance sheet, pipeline updates):
• Earnings call transcript (prepared remarks and Q&A):
• Prior quarter comparisons: Q4 2024 8-K ; Q3 2024 8-K
• Other relevant press releases (Q1/Q2 timing but relevant to Q1 context): LUCIDITY first patient dosed ; LUMINA first patient dosed ; FDA lifted hold on AMX0114 .*