Amylyx Pharmaceuticals, Inc. · NASDAQ:AMLX
Amylyx Pharmaceuticals — Investor Presentation (September 2026)
38 slides from Amylyx Pharmaceuticals's investor presentation, September 2026
Slide 1: September 2026 Corporate Presentation
SEPTEMBER 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 AVEXITIDE Post-Bariatric • NDA submission to the FDA expected by
Slide 4: Avexitide
AVEXITIDE Investigational, First-in-Class GLP-1 Receptor Antagonist with FDA Breakthrough Therapy Designation Pancreatic islet cells
Slide 5: 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 in PBH and Orphan Drug Designation • Phase 3 LUCIDITY trial of avexitide in post-bariatric hypoglycemia (PBH) following RYGB surgery met its primary and all secondary endpoints > 55% reduct
Slide 6: Avexitide Targets a Central Pathway of PBH Pathophysiology
Avexitide, an Investigational, 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 Altered Stomach Results in Recurrent, Rapid GLP-1 Receptor and Pro
Slide 7: Phase 3 LUCIDITY Trial Design
Phase 3 LUCIDITY Trial Design PHASE 3 LUCIDITY TRIAL DESIGN - Multicenter, randomized, double-blind, placebo-controlled trial (N=78) 16-week Double-blind Treatment Period 32-week Open-label Extension Period 3:2 Randomization Avexitide 90 mg Once Daily N=78 21-day Eligibility Run-in Period Avexitide
Slide 8: LUCIDITY Met Primary Endpoint
LUCIDITY Met Primary Endpoint Statistically significant 55% reduction in composite rate of Level 2 and Level 3 hypoglycemic events compared to placebo Composite Level 2/3 Hypoglycemic Event Rate 100 Reduction vs. Placebo, Week 16 (ITT, N=78) 90 LUCIDITY Met All Secondary Endpoints LS Mean % Reductio
Slide 9: Avexitide Generally Well-Tolerated with a Favorable Safety Profile Through 16 Weeks
Avexitide was Generally Well-Tolerated with a Favorable Safety Profile Through 16 Weeks • Adverse events were generally mild or moderate • No treatment-related serious adverse events • Most common adverse events were diarrhea, injection site erythema, and injection site bruising • No changes in body
Slide 10: Five Clinical Trials of Avexitide Demonstrate Statistically Significant Results in PBH
Five Clinical Trials of Avexitide Demonstrate Statistically Significant Results in PBH Consistent with LUCIDITY % 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 Squares Mean) 60% 57% p=0.0003 p=0
Slide 11: Avexitide has the Potential to be a First FDA-approved Treatment for PBH
Avexitide has the Potential to be a First FDA-approved Treatment for PBH Phase 3 LUCIDITY Trial Topline Data Summary Patient Impact 1 Avexitide met primary and secondary endpoints 1 Preventing a single Level 2 or Level 3 hypoglycemic demonstrating statistically significant and event could enable som
Slide 12: Post-Bariatric Hypoglycemia: A Chronic, Debilitating Condition with High Unmet Need
Post-Bariatric Hypoglycemia (PBH): A Chronic, Debilitating Condition with High Unmet Need PBH Can be Dangerous and Life-Altering • Hypoglycemic events can cause cognitive Maria, living with PBH impairment, loss of consciousness, and even seizures because the brain is not getting enough glucose (neur
Slide 13: PBH has Significant Unmet Need with no Approved Treatment Options
PBH has Significant Unmet Need with no Approved Treatment Options ~160,000 people Currently living with Rate of Gastric Bypass by Type PBH in the U.S.1 350,000 300,000 No approved 250,000 BETWEEN 2013-2023 treatment options 200,000 Sleeve.....~1.4 million 150,000 100,000 RYGB......~0.6 Million ~200K
Slide 14: ~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 15: Phase 3 LUCIDITY Positive Topline Results Advance Potential Commercial Launch of Avexitide
Phase 3 LUCIDITY Positive Topline Results Advance Potential Commercial Launch of Avexitide Leadership team tenured in rare disease, global regulatory approval, and commercial launch experience 2027 Strong IP position with patent rights through 2037, potential for By End of 2026 Anticipated additio
Slide 16: 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 17: 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 18: 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 19: 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 20: 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 21: 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 22: 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 AUC change from baseline at 120 Minutes Improvement & 60 34.5 (SE: 13.0; in C-Peptide Response 50 p=0.0263) Obser
Slide 23: 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 24: 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)* > Diarrhea was the most common TEAE n (%) (58.3%); all cases were of mild severity Participants with ≥1 TEAE 11 (91.7) > All TEAEs were graded mild or
Slide 25: 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 26: AMX0114: ASO Targeting Knockdown of Calpain-2 for the 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 speak, respiratory paralysis, and death1,2 • ALS affects as many as 30,000 adults in the U.S.3 PROGRAM MILESTONES o >90% of
Slide 27: Axonal Degeneration Disrupts Neural Connectivity and is a Key Early Contributor to 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 28: Calpain-2 Plays an Essential Role in Axonal Degeneration in ALS
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 29: AMX0114 Reduces Extracellular NfL Levels and Improves Survival in Relevant 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 30: LUMINA: Phase 1 Clinical Trial of AMX0114 in ALS
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 from baseline in neurofilament light (NfL) levels Cohort 4 (Pla
Slide 31: AMX0318
AMX0318 Novel, Long-Acting GLP-1 Receptor Antagonist
Slide 32: 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 33: Key Corporate Highlights
YrAMYLYX Key Corporate Highlights
Slide 34: Advancing Novel Therapies for Diseases with High Unmet Needs
Advancing Novel Therapies for Diseases with High Unmet Needs Focus on diseases with well-defined mechanistic rationale, clear clinical outcomes and biomarkers, and rigorous preclinical data 2027 2027 By End of 2026 Anticipated AMX0318 IND-enabling studies underway with EXPECTED Expected avexitide av
Slide 35: 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 >250 >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 36: Public Offering
Public Offering Closed on August 21, 2026 As of June 30, 2026 Net Proceeds $250.8M $544.5M in cash, cash equivalents and marketable securities PRO FORMA SHARES OUTSTANDING AFTER OFFERING* 127.6M *As noted in Form 424B5 filed Aug. 20, 2026 36
Slide 37: 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 2013. Co-fou
Slide 38: Ushering in a New Era for Treating Diseases with High Unmet Needs
Ushering in a New Era for Treating Diseases with High Unmet Needs
Amylyx Pharmaceuticals — Investor Presentation (September 2026) on 6ix