Amylyx Pharmaceuticals, Inc. · NASDAQ:AMLX
Amylyx Pharmaceuticals — Investor Presentation (March 2026)
41 slides from Amylyx Pharmaceuticals's investor presentation, Mar 24, 2026
Slide 1: Audacious mission to develop novel therapies for high unmet needs
Exhibit 99.1 MARCH 2026 We have an audacious mission to develop novel therapies for diseases with high unmet needs, with a focus on serious and fatal endocrine conditions and neurodegenerative diseases. 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 • Phase 3 LUCIDITY trial underway. Enrollment completed. Topline
Slide 4: Avexitide: First-in-Class GLP-1 Receptor Antagonist with FDA Breakthrough Therapy Designation
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 is evaluating the FDA-agreed EXPECTED MILESTONE upon primary outcome of reduction in the composite of Leve
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 Hypersecretion of Insulin Avexitide Binds to Mitigates Insulin Hypersecretion Results in Recurrent, Rapid GLP-1 Receptor and Promotes Glucose Altered Stomach Drop
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 (mg/dL, mean ± SEM) Proof of Concept in People (μU/mL, mean ± SEM) 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 100 90 Level 2 Level 3 68% 66% Avexitide cut rates of 80 p=0.0003 60% p=0.0003 70 57% hypoglycemic events by 56% p=0.004 53% p=0.01 p=0.003 60 p=0.004 40%
Slide 10: Avexitide Reduced Composite Level 2 and 3 Hypoglycemia in Exploratory Analysis
Avexitide Significantly Reduced Rates of Composite Level 2 and 3 FDA Breakthrough Hypoglycemia in Exploratory Analysis Therapy Designation % Reduction in Rate of Hypoglycemia by Avexitide Dose % Reduction in Composite Phase 3 program will 100 a b evaluate 90 mg once Rate of Level 2 and 90 Level 2 Le
Slide 11: Exploratory Analysis Using the Phase 3 LUCIDITY Primary Endpoint Model
Exploratory Analysis of Prior Trials Showed Statistically Significant Results Using the Phase 3 LUCIDITY Primary Endpoint Model 1 Table 1. Reduced Rates of Composite Level 2 and 3 Hypoglycemia in Phase 2 PREVENT Study Screening Period Run-In Period Avexitide 30 mg Avexitide 60 mg Key Takeaways Place
Slide 12: Avexitide Reproducibly Improved Insulin and Glucose Responses
CONSISTENT RESULTS IN PBH CLINICAL TRIALS Avexitide Reproducibly Improved Insulin and Glucose Responses During Standardized Meal Tests in People with PBH 1 2 3 4 Phase 1 SAD MAD Phase 2 PREVENT Avexitide Avexitide Avexitide Avexitide Avexitide IV infusion SC injection 30 mg BID 30 mg BID 60 mg QD SC
Slide 13: Avexitide Generally Well-Tolerated with Favorable Safety Profile
Avexitide was Generally Well-Tolerated with a Favorable Safety Profile Across Both Phase 2 Trials 1 2 Phase 2 PREVENT Study Phase 2b Study AEs generally mild to moderate and AEs generally mild to moderate and transient transient No clinically meaningful increases were observed in No treatment-relate
Slide 14: Phase 3 LUCIDITY Trial Design 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 15: 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 16: Post-Bariatric Hypoglycemia is 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 ~160,000 >200K Dangerous and Life-Altering people new procedures • General fatigue, confusion, difficulty 1 occur annually Curre
Slide 17: ~160K People Live With PBH in U.S.
Source Finding 2.5M bariatric surgeries of which 2M were either sleeve gastrectomy ~160K People Live With PBH in U.S. 1a ASMBS Registry of Bariatric Surgery (SG) or Roux-en-Y gastric bypass (RYGB) 56.1% prevalence of hypoglycemia in studies specifically examining 2 8-Study Meta-Analysis (N=280) RYGB
Slide 18: 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 Anticipated Q3 2026 additional term through commercial Expected March 2026 Patent Term Extensions launch in 2027, pivotal study Enrollment April 2025 if approved readou
Slide 19: AMX0035 Fixed-Dose Combination of Sodium Phenylbutyrate and Taurursodiol
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 20: 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 Primary efficacy outcome of improvement in pancreatic by targeting ER stress and function at Week 24 met in Pha
Slide 21: Wolfram Syndrome is a Rare, Fatal, Monogenic, Progressive Disorder
1-5 Wolfram Syndrome is a Rare, Fatal, Monogenic, Progressive Disorder 1-5 WFS1 GENE MUTATION PROGRESSIVELY IMPACTS MULTIPLE ORGANS AND SYSTEMS ~3,000 people Living with Wolfram 1,2 Syndrome in the U.S. No approved therapies 6 for Wolfram syndrome Childhood-onset Gradual Loss of Diabetes Insipidus H
Slide 22: Wolfram Syndrome is a Prototypical ER Stress Disorder
1 Wolfram Syndrome is a Prototypical Endoplasmic Reticulum (ER) Stress Disorder AMX0035 targets ER stress and related mitochondrial dysfunction pathways SODIUM PHENYLBUTYRATE (PB) TAURURSODIOL (TURSO) Stabilizes protein conformation Targets Bax, reduces 3,4 5,6 during folding mitochondrial driven ce
Slide 23: 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 Safety OPEN-LABEL TREATMENT PERIOD EXTENSION TREATMENT PERIOD Period Follow-up (48 weeks) (160 weeks) 4 weeks 4 weeks Week 24 Week 48 Results showed improve
Slide 24: 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 Progressive Decline C-Peptide Response
Slide 25: 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 34.5 & 60 in C-Peptide Response (SE: 13.0;
Slide 26: AMX0035 Reduced Overall Symptom Burden
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 27: 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 28: AMX0114 Potent Antisense Oligonucleotide Targeting Calpain-2
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 29: AMX0114: ASO Targeting Calpain-2 for Potential Treatment of 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 1,2 speak, respiratory paralysis, and death EXPECTED MILESTONES 3 • ALS affects as many as 30,000 adults in the U.S. o >90%
Slide 30: Axonal Degeneration is a Key Early Contributor to ALS Pathogenesis
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 31: 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, 1-4 Evidence for Targeting Calpain-2 in ALS as a Target with Increased NfL Fragments Seen i
Slide 32: AMX0114 Reduces Extracellular NfL and Improves Survival in Models
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 33: 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 34: AMX0318 Novel, Long-Acting GLP-1 Receptor Antagonist
AMX0318 Novel, Long-Acting GLP-1 Receptor Antagonist
Slide 35: 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 EXPECTED MILESTONES development candidate • AMX0318 comp
Slide 36: Key Corporate Highlights
YAMYLYX Key Corporate Highlights
Slide 37: Advancing Novel Therapies: Expected Upcoming Milestones
Advancing Novel Therapies for Diseases with High Unmet Needs Expected Upcoming Milestones Focus on diseases with well-defined mechanistic Phase 3 LUCIDITY topline data Q3 2026 Avexitide PBH Clinical anticipated in Q3 2026 rationale, clear clinical outcomes and biomarkers, and rigorous preclinical da
Slide 38: Protected by Robust Global IP Portfolio
Avexitide, AMX0035, and AMX0114 are Protected by Robust Global IP Portfolio AVEXITIDE AMX0035 AMX0114 granted patents and over granted patents and over Pending composition of matter 40 pending applications 50 pending applications patent provides potential patent >80 >200 worldwide* worldwide term th
Slide 39: Cash Runway Expected Into 2028
As of December 31, 2025 CASH RUNWAY EXPECTED INTO 2028 • $317M in cash, cash equivalents, and short-term investments THROUGH THE POTENTIAL APPROVAL • ~110M shares outstanding AND LAUNCH OF AVEXITIDE IN 2027 39
Slide 40: Leadership 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 41: 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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