Amylyx Pharmaceuticals, Inc. · NASDAQ:AMLX
Amylyx Pharmaceuticals — Q4 2025 Earnings Presentation
40 slides from Amylyx Pharmaceuticals's earnings presentation, Mar 3, 2026
Slide 1: We have an audacious mission to develop novel therapies
MARCH 2026 We have an audacious mission to develop novel therapies for diseases with high unmet needs, with a focus on serious and fatal neurodegenerative diseases and endocrine conditions. Maggie, a mom and advocate living with post-bariatric hypoglycemia (PBH). Pancreatic islet cells
Slide 2: Disclaimer
DISCLAIMER Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results
Slide 3: A Growing Pipeline of Therapies to Serve Communities with High Unmet Needs
A Growing Pipeline of Therapies to Serve Communities with High Unmet Needs Led by an experienced team with a proven track record of commercialization in rare diseases IND-ENABLING PRECLINICAL PHASE 1 PHASE 2 PHASE 3 COMMERCIAL STUDIES AVEXITIDE Post-Bariatric Hypoglycemia • Phase 3 LUCIDITY trial un
Slide 4: Avexitide
AVEXITIDE Investigational, First-in-Class GLP-1 Receptor Antagonist with FDA Breakthrough Therapy Designation Pancreatic islet cells
Slide 5: Avexitide: Investigational, First-in-Class GLP-1 Receptor Antagonist
Avexitide: Investigational, First-in-Class GLP-1 Receptor Antagonist • FDA Breakthrough Therapy Designation and Orphan Drug Designation in hyperinsulinemic hypoglycemia • Phase 3 LUCIDITY trial designed to evaluate FDA- EXPECTED MILESTONE agreed upon primary outcome of reduction in hypoglycemic even
Slide 6: Avexitide Targets a Central Pathway of PBH Pathophysiology
Avexitide, a First-in-Class GLP-1 Receptor Antagonist, Targets a Central Pathway of PBH Pathophysiology GLP-1 Receptor Antagonism 1 2 3 4 Hyper-secretion of Insulin Avexitide Binds to Mitigates Insulin Hypersecretion Altered Stomach Results in Recurrent, Rapid GLP-1 Receptor and Promotes Glucose Dro
Slide 7: Targeted Approach to Inhibit Effects of Excessive GLP-1 in PBH
Targeted Approach to Inhibit Effects of Excessive GLP-1 in PBH to Mitigate Hypoglycemia GLP-1 levels observed to be more than 10-fold Avexitide inhibits GLP-1 receptor activity and higher in PBH than in Nonsurgical Controls, decreases the insulin response to glucose in rat resulting in dysregulated
Slide 8: Clinical Data Underscores the Critical Role of GLP-1 in PBH
Clinical Data Underscores the Critical Role of GLP-1 in PBH and Supports the Potential of GLP-1 Receptor Antagonism as a Targeted Approach Insulin Glucose (μU/mL, mean ± SEM) (mg/dL, mean ± SEM) Proof of Concept in People with PBH (N=8) Demonstrated: Placebo Placebo • 100% prevention of Avexitide A
Slide 9: Avexitide Significantly Reduced Rates of Hypoglycemia in Two Phase 2 Trials
Avexitide Significantly Reduced Rates of Hypoglycemia in Two Phase 2 Clinical Trials in PBH % Reduction in Rate of Hypoglycemia by Avexitide Dose % Reduction in Rate of Hypoglycemia 100 90 Level 2 Level 3 80 68% 66% Avexitide cut rates of (Least Squared Mean) 60% 57% p=0.0003 p=0.0003 hypoglycemic e
Slide 10: Avexitide Reduced Rates of Composite Level 2 and 3 Hypoglycemia
Avexitide Significantly Reduced Rates of Composite Level 2 and 3 Hypoglycemia in New Exploratory Analysis FDA Breakthrough Therapy Designation % Reduction in Rate of Hypoglycemia by Avexitide Dose % Reduction in Composite Phase 3 program will % Reduction in Rate of Hypoglycemia 100 Ratea of Level 2b
Slide 11: Avexitide Reproducibly Improved Insulin and Glucose Responses During Meal Tests
CONSISTENT RESULTS IN PBH CLINICAL TRIALS Avexitide Reproducibly Improved Insulin and Glucose Responses During Standardized Meal Tests in People with PBH Phase 11 SAD2 MAD3 Phase 2 PREVENT4 Avexitide Avexitide Avexitide Avexitide Avexitide IV infusion SC injection 30 mg BID 30 mg BID 60 mg QD (n=8)
Slide 12: Avexitide Generally Well-Tolerated with Favorable Safety Profile
Avexitide was Generally Well-Tolerated with a Favorable Safety Profile Across Both Phase 2 Trials Phase 2 PREVENT Study1 Phase 2b Study2 AEs generally mild to moderate and AEs generally mild to moderate and transient transient No clinically meaningful No treatment-related serious AEs increases were
Slide 13: Phase 3 LUCIDITY Trial Designed to be Consistent with Phase 2 Trials
Phase 3 LUCIDITY Trial Designed to be Consistent with Phase 2 PREVENT and Phase 2b Trials Evaluating Avexitide for the Treatment of PBH PHASE 2 PREVENT TRIAL DESIGN - 28-day, randomized, placebo-controlled crossover trial (N=18) 14-day Treatment Period 14-day Treatment Period 14-day Treatment Period
Slide 14: Phase 3 LUCIDITY Trial Design Elements Compared
Phase 3 LUCIDITY Trial Designed to be Consistent with Phase 2 PREVENT and Phase 2b Trials Evaluating Avexitide for the Treatment of PBH STUDY DESIGN ELEMENTS PHASE 2 PREVENT PHASE 2B PHASE 3 LUCIDITY RYGB RYGB RYGB Sleeve gastrectomy, Study Population: Surgery Esophagectomy, Nissen fundoplication, G
Slide 15: PBH is Believed to be Caused by Excessive GLP-1 Response
Post-Bariatric Hypoglycemia (PBH) is Believed to be Caused by Excessive GLP-1 Response that Leads to Hyperinsulinemic Hypoglycemia Post-Meal Hypoglycemia from PBH is Often Dangerous and Life-Altering ~160,000 >200K people new procedures • General fatigue, confusion, difficulty occur annually1 Curren
Slide 16: ~160K People Live With PBH in U.S.
~160K People Live With PBH in U.S. Source Finding 2.5M bariatric surgeries of which 2M were either sleeve gastrectomy ASMBS Registry of Bariatric Surgery1a (SG) or Roux-en-Y gastric bypass (RYGB) 56.1% prevalence of hypoglycemia in studies specifically examining 8-Study Meta-Analysis (N=280)2 RYGB a
Slide 17: Phase 3 LUCIDITY Trial Underway, Readout Expected in Q3 2026
Phase 3 LUCIDITY Trial Underway, Readout Expected in Q3 2026 Strong IP position with patent rights through 2027 2037, potential for Q3 2026 Anticipated commercial additional term through Q1 2026 Expected Patent Term Extensions pivotal study launch in 2027, April 2025 Randomize if approved readout in
Slide 18: AMX0035
AMX0035 Fixed-Dose Combination of Sodium Phenylbutyrate and Taurursodiol Designed to Slow or Mitigate Neurodegeneration Raquel, a college student and martial artist living with Wolfram syndrome. Retinal ganglion cells
Slide 19: AMX0035 for the Potential Treatment of Wolfram Syndrome
AMX0035 for the Potential Treatment of Wolfram Syndrome Focused on studying AMX0035 in Wolfram syndrome, a prototypical ER stress disorder AMX0035 is designed to mitigate neurodegeneration by targeting ER stress and Primary efficacy outcome of improvement in pancreatic function at Week 24 met in Pha
Slide 20: Wolfram Syndrome is a Rare, Fatal, Monogenic, Progressive Disorder
Wolfram Syndrome is a Rare, Fatal, Monogenic, Progressive Disorder1-5 WFS1 GENE MUTATION PROGRESSIVELY IMPACTS MULTIPLE ORGANS AND SYSTEMS1-5 ~3,000 people Living with Wolfram Syndrome in the U.S.1,2 No approved therapies for Wolfram syndrome6 Childhood-onset Gradual Loss of Diabetes Insipidus Heari
Slide 21: Wolfram Syndrome is a Prototypical ER Stress Disorder
Wolfram Syndrome is a Prototypical Endoplasmic Reticulum (ER) Stress Disorder1 AMX0035 targets ER stress and related mitochondrial dysfunction pathways SODIUM PHENYLBUTYRATE (PB) TAURURSODIOL (TURSO) Stabilizes protein conformation Targets Bax, reduces during folding3,4 mitochondrial driven cell dea
Slide 22: HELIOS Study Design
HELIOS Study Design Open-label, single-arm clinical trial of AMX0035 in people with Wolfram syndrome, enrolling up to 12 participants Screening OPEN-LABEL TREATMENT PERIOD EXTENSION TREATMENT PERIOD Safety Period Follow-up (48 weeks) (160 weeks) 4 weeks Week 24 Week 48 4 weeks Results showed improve
Slide 23: Long-Term Data Suggest Potential Benefit of AMX0035 in Wolfram Syndrome
Long-Term Data Suggest Potential Benefit of AMX0035 in Wolfram Syndrome Across Multiple Outcomes Related to Disease Progression Expected Progression of Wolfram Syndrome Trend Baseline to Week 24 Trend Baseline to Week 48 Partial Reversal in Partial Reversal in C-Peptide Response AUC Progressive Decl
Slide 24: Primary Endpoint: Improvement in C-Peptide Response Observed
Primary Endpoint: Improvement in C-Peptide Response Observed Overall increase in mean C-peptide production from 0-120 minutes during MMTT* C-Peptide Response to Mixed Meal Tolerance Test JOINT CONGRESS OF AUC change from baseline at 120 Minutes Improvement & 60 34.5 (SE: 13.0; in C-Peptide Response
Slide 25: AMX0035 Reduced Overall Symptom Burden at Week 24 and Week 48
AMX0035 Reduced Overall Symptom Burden at Week 24 and Week 48 Qualitative on-study interview results support potential positive impact of AMX0035 on symptom burden Positive Changes in Wolfram Syndrome-Related Symptoms by Participant Report in On-Study Interviews Vision Problems (n=11) Bladder Issues
Slide 26: AMX0035 Safety and Tolerability in HELIOS
AMX0035 Safety and Tolerability in HELIOS Summary of Treatment Emergent Adverse Events (TEAEs) AMX0035 • AMX0035 was generally well tolerated (N=12)* n (%) > Diarrhea was the most common TEAE (58.3%); all cases were of mild severity Participants with ≥1 TEAE 11 (91.7) > All TEAEs were graded mild or
Slide 27: AMX0114
AMX0114 Potent Antisense Oligonucleotide (ASO) Targeting Calpain-2 In memory of Mick, a husband and father, who was a gifted tattoo artist and musician. Nerve cells in the brain
Slide 28: AMX0114: ASO Targeting Knockdown of Calpain-2 for ALS
AMX0114: Antisense Oligonucleotide (ASO) Targeting Knockdown of Calpain-2 for the Potential Treatment of ALS • ALS leads to deteriorating muscle function, inability to move and speak, respiratory paralysis, and death1,2 EXPECTED MILESTONES • ALS affects as many as 30,000 adults in the U.S.3 o >90% o
Slide 29: Axonal Degeneration Disrupts Neural Connectivity in ALS
Axonal Degeneration Disrupts Neural Connectivity and is a Key Early Contributor to the Pathogenesis of ALS Mechanisms of Axonal Degeneration Excess activation of glutamatergic, nicotinic, or voltage gated calcium channels drive influx of calcium from the extracellular space into cell Oxidative or is
Slide 30: Calpain-2 Plays an Essential Role in Axonal Degeneration
Calpain-2, a Protein Involved in Neurofilament Biology, Plays an Essential Role in Axonal Degeneration, a Critical Effector in the Progression of ALS Genetic Support for Calpain-2 NfL is Cleaved by Calpain-2, Evidence for Targeting Calpain-2 in ALS1-4 as a Target with Increased NfL Fragments Seen in
Slide 31: AMX0114 Reduces Extracellular NfL Levels in Models of Neuronal Injury
AMX0114 Reduces Extracellular NfL Levels in Multiple Models of Trigger-Induced Neuronal Injury and Improves Survival in Relevant Models Pretreatment with AMX0114 Reduces Extracellular Pretreatment with AMX0114 improves motor neuron AMX0114 Treatment Improves Motor Neuron Survival in TDP43 ALS iPSC M
Slide 32: LUMINA: Phase 1 Clinical Trial of AMX0114 in ALS
LUMINA UNDERWAY; COHORT 1 BIOMARKER DATA EXPECTED IN 1H 2026 LUMINA: Phase 1 Clinical Trial of AMX0114 in ALS PRIMARY OBJECTIVE: To assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMX0114 in people living with ALS • Will assess ALS biomarkers, including change fr
Slide 33: AMX0318
AMX0318 Novel, Long-Acting GLP-1 Receptor Antagonist
Slide 34: AMX0318: A Novel, Long-Acting GLP-1 Receptor Antagonist
AMX0318: A Novel, Long-Acting Glucagon-Like Peptide-1 (GLP-1) Receptor Antagonist • Entered into a collaboration with Gubra A/S in December 2024 to develop a long-acting GLP-1 receptor antagonist and in January 2026, AMX0318 was nominated as a development candidate EXPECTED MILESTONES • AMX0318 comp
Slide 35: Key Corporate Highlights
YYAMYLYX’ Key Corporate Highlights
Slide 36: Advancing Novel Therapies for Diseases with High Unmet Needs
Advancing Novel Therapies for Diseases with High Expected Upcoming Milestones Unmet Needs Q1 2026 Avexitide PBH Clinical Phase 3 LUCIDITY recruitment complete and expect to randomize and dose last eligible participants in Q1 2026 Focus on diseases with well-defined mechanistic rationale, clear clini
Slide 37: Avexitide, AMX0035, and AMX0114 are Protected by Robust Global IP Portfolio
Avexitide, AMX0035, and AMX0114 are Protected by Robust Global IP Portfolio AVEXITIDE AMX0035 AMX0114 >200 >80 granted patents and over granted patents and over Pending composition of matter 40 pending applications 50 pending applications patent provides potential patent worldwide* worldwide term th
Slide 38: Cash Runway Expected into 2028
CASH RUNWAY As of December 31, 2025 EXPECTED INTO 2028 • $317M in cash, cash equivalents, and short-term investments THROUGH THE POTENTIAL APPROVAL AND LAUNCH OF AVEXITIDE IN 2027 • ~110M shares outstanding 38
Slide 39: Team
Team Leadership Team Tenured in Rare Disease with Commercial and Clinical Development Capabilities Joshua Cohen, BSE Justin Klee, ScB Jim Frates Camille L. Bedrosian, MD Co-CEO and Director Co-CEO and Director Chief Financial Officer Chief Medical Officer Co-Founded Amylyx, Co-CEO since Co-Founded A
Slide 40: Ushering in a New Era for Treating Diseases with High Unmet Needs
Ushering in a New Era for Treating Diseases with High Unmet Needs
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