Amylyx Pharmaceuticals, Inc. Q4 FY2025 earnings call

Good morning, everyone. Lindsay Allen welcomes to discuss fourth quarter and full year 2025 financial results and business updates. Justin Klee mentions in 2025, advanced pipeline, made progress on Avexotide's regulatory and commercial preparations, strengthened financial position with cash runway into 2028, and positioned for 2026. Initiated pivotal phase three lucidity trial of Exotide. Collaboration with Gubra progressed. AMX114 got fast track designation and favorable safety/tolerability in ALS phase one trial. Camille Bedrosian discusses PBH, the lucidity trial, and launch preparations. Jim Fradies reviews financials: ended Q4 with $317M in cash/marketable securities, operating expenses down 8% Q4 2025, R&D down due to AMX 35 spending decrease offset by Avexatide spending increase, SG&A down. Josh Cohen talks about broader pipeline strategy, AMX318's IND-enabling studies, AMX114's phase one Lumina trial progress, and AMX35's work with FDA.

One, deliver top line data from pivotal phase three lucidity trial expected in Q3 2026 with recruitment complete and on track to fully complete enrollment this quarter. Two, advance NDA readiness and regulatory preparations. Three, strengthen launch readiness to support potential 2027 commercialization of Avexatide. Also, AMX318's IND filing targeted for 2027. AMX114 to present biomarker data from cohort one of phase one Lumina trial in ALS in first half of 2026.

Q: Learnings from execution of lucidity trial, specifically recruitment and powering.

A: Inclusion criteria informed by prior trials, unmet need underscored, broad participation, powering conservative.

Q: Follow-up on commercial prep from Lucidity and OLE.

A: Commercial prep includes market research, corroborating patient numbers, OLE participants rolling over.

Q: Checking claims database data.

A: Pressure tested claims data, validated epidemiology and patient locations.

Q: Vectortide Phase 2B trial non-responders.

A: Saw strong effect, some variability but response across cohort.

Q: Commercial and severe PBH patients.

A: Physicians see all events as medical emergencies, unmet need.

Q: Meaningful reduction in hypoglycemic episodes.

A: Physicians want reduction, statistically significant data needed.

Q: Baseline characteristics from lucidity before Q3.

A: Still considering, focus on Q3 data.

Q: 318 timing and indications.

A: Excited about 318, moving ahead, GLP-1 antagonism for various surgeries.

Q: Market opportunity and Acarbose.

A: Acarbose not FDA approved for PBH, not well tolerated, doesn't target root cause.

Q: ICD-10 code for PBH.

A: ICD-10 code shows growing awareness, helps in claims and care.

Q: Events in lucidity trial and clinician focus.

A: Clinicians view level two as risky, events skew with composite endpoint.

Q: Diet in lucidity trial and GLP-1 blockade effectiveness.

A: Diet training provided, GLP-1 blockade effective with large carbohydrate load.

Q: Avexatide tolerability and Gubra asset.

A: Avexatide tolerability excellent, Gubra asset evaluated for immunogenicity, etc.