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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
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 may
differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, the Company's plans to explore the use of avexitide as a treatment for post-bariatric hypoglycemia (PBH) and
congenital hyperinsulinism, AMX0035 for Wolfram syndrome, AMX0114 for ALS, and AMX0318 for PBH and other rare diseases; statements regarding the timing of clinical trials for PBH, Wolfram syndrome and/or ALS; expectation for regulatory action; and
expectations regarding our longer-term strategy and expected cash runway. Any forward-looking statements in this presentation are based on management's current expectations of future events and are subject to a number of risks and
uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward- looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the
success, cost, and timing of Amylyx' program development activities, including ongoing and planned clinical trials, Amylyx' ability to execute on its development and regulatory strategy, regulatory developments, Amylyx' cash runway
and ability to fund operations, as well as the risks and uncertainties set forth in Amylyx' United States Securities and Exchange Commission (SEC) filings, including Amylyx' Annual Report on Form 10-K for the year ended December 31,
2024, and subsequent filings with the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or
circumstances that exist after the date on which they were made. 2
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. Topline data expected in Q3 2026,
Post-Bariatric AVEXITIDE and if approved, commercial launch anticipated in 2027 Hypoglycemia LUCIDITY PHASE 3 CLINICAL TRIAL Inhibitor of GLP-1 FDA-agreed upon primary outcome of reduction in hypoglycemic (PBH) receptor activity events FDA
Breakthrough Congenital Therapy and Orphan Engaging physician and community experts around next steps Hyperinsulinism Drug Designations for clinical development (HI) Pending alignment with the FDA, plan to initiate a focused, pivotal
Phase 3 trial of AMX0035 in Wolfram syndrome AMX0035 Wolfram Positive Phase 2 HELIOS data showed improvement or stabilization HELIOS PHASE 2 CLINICAL TRIAL Sodium phenylbutyrate and Syndrome across all disease measures at Week 24 (N=11) and
sustained taurursodiol (also known as improvement or stabilization at Week 48 (N=10) ursodoxicoltaurine) Early data from cohort 1 (n=12) demonstrated AMX0114 was generally well-tolerated, with no treatment-related SAEs in Phase 1 AMX0114
Amyotrophic LUMINA trial ASO targeting calpain-2, a Lateral Sclerosis LUMINA PHASE 1 CLINICAL TRIAL protein involved in axonal Began enrolling cohort 2 (n=12) in December 2025 (ALS) degeneration Granted FDA Fast Track designation
As part of research collaboration with Gubra, AMX0318 demonstrated a robust chemical stability profile, strong in vitro potency, evidence of AMX0318 in vivo efficacy and tolerability, high solubility, and a favorable PBH and Other
pharmacokinetic profile consistent with a long-acting peptide Long-acting GLP-1 Rare Diseases receptor antagonist Expected to advance into IND-enabling studies in 2026, and pending successful completion of IND-enabling studies, IND expected
in 2027 ASO=antisense oligonucleotide; FDA=U.S. Food and Drug Administration; GLP-1=glucagon-like peptide-1; IND=investigational new drug; SAE=serious adverse events. 3
AVEXITIDE Investigational, First-in-Class Inhibitor of GLP-1 Receptor
Activity with FDA Breakthrough Therapy Designation Pancreatic islet cells
Avexitide: Investigational, First-in-Class Inhibitor of GLP-1 Receptor
Activity FDA Breakthrough Therapy Designation and Orphan Drug Designation in hyperinsulinemic hypoglycemia EXPECTED MILESTONES Phase 3 LUCIDITY trial designed to evaluate FDA- agreed upon primary outcome of reduction in Began Dosing
in Avexitide APRIL 2025 hypoglycemic events in PBH following RYGB surgery Phase 3 Trial in PBH (Complete) Prior clinical studies generated highly statistically significant reductions in hypoglycemic events Complete Recruitment of
Avexitide Phase 3 PBH is an orphan condition that is often life-altering; Q1 2026 Trial in PBH ~160,000 prevalent patients Strong IP position with patent rights through 2037 Topline Data from Avexitide and potential for patent term
extension Q3 2026 Phase 3 Trial in PBH FDA=U.S. Food and Drug Administration; GLP-1=glucagon-like peptide-1; IND=Investigational New Drug; IP=intellectual property; PBH=post-bariatric hypoglycemia; RYGB=Roux-en-Y gastric bypass 5
Avexitide, a First-in-Class Inhibitor of GLP-1 Receptor Activity,
Targets a Central Pathway of PBH Pathophysiology Inhibition of GLP-1 Receptor Activity 1 2 3 4 Hyper-secretion of Insulin Avexitide Binds to Mitigates Insulin Hypersecretion Results in Recurrent, Rapid GLP-1 Receptor and Promotes Glucose Altered
Stomach Drops in Blood Glucose Stabilization Insulin Pancreas GLP-1 Islet Insulin Beta Cells Receptor Intestine Stable Blood Meal Meal GLP-1 Glucose Response +10x increase Avexitide in GLP-1 Rapid Drop in Blood Glucose levels TIME TIME Altered
nutrient transit This exaggerated GLP-1 Avexitide binds to the GLP-1 Decreased insulin secretion due to anatomical changes secretion leads to abnormally receptor on pancreatic islet and stabilized glucose associated with bariatric surgery high
insulin levels in the beta cells to inhibit the levels resulting from (e.g., Roux-en-Y gastric bypass) bloodstream, and subsequent effect of exaggerated inhibition of the effect of leads to exaggerated GLP-1 hypoglycemia GLP-1 exaggerated GLP-1
secretion in people with PBH GLP-1=glucagon-like peptide-1; PBH=post-bariatric hypoglycemia; 1. Sheehan A, Patti ME. Diabetes Metab Syndr Obes. 2020;13:4469-4482; 2. Craig CM, et al. Diabetes Obes Metab. 2017; 1-10. 3. Thorens B,. et al.
Diabetes.1993;42(11):1678-1682. 4. Craig CM, et al. Diabetes Obes Metab. 2018;20(2):352-361. 5. Smith NK, et al. Neurochem Int. 2019;128:94-105. 6. 6 Meloni AR, et al. Diabetes Obes Metab. 2013;15(1):15-27. 7. Craig CM, et al. Diabetologia.
2017;60(3):531-540. 8. Craig C, et al. J Endocr Soc. 2022;6(Suppl 1):A349. BLOOD SUGAR LEVEL BLOOD SUGAR LEVEL
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 secretion of
insulin and 1,2, 3 pancreatic islet cells subsequent hypoglycemia 300 4 Gastric Bypass + PBH (GB + PBH) 16.7 G +/- GLP-1 +/- Avexitide Gastric Bypass (GB) Overweight (OW) Morbidly Overweight (Mob) 200 Glucose Glucose + GLP-1 Glucose + GLP-1 +
Avexitide 100 Glucose + GLP-1 + Avexitide 0 0 20 40 60 80 100 120 Time (min) Time (min) GLP-1=glucagon-like peptide-1; GSIS=glucose-stimulated insulin secretion; PBH=post-bariatric hypoglycemia; 1. Goldfine A. B. et al. J Clin Endocrinol Metab.
2007; 92(12):4678-4685. doi.org/10.1210/jc.2007- 0918. 2. Cabrera O. et al. The Journal of Biological Chemistry. 2022;298(2):101484. doi:10.1016/j.jbc.2021.101484; 3. Averaged data from five independent experiments; 4. Step-wise increase of
glucose concentration from 2.8 to 16.7 mM (2.8G and 16.7G). 7 GLP-1 (pmol/L) Insulin (ng) / DNA ( g)
Clinical Data Underscores the Critical Role of GLP-1 in PBH and Supports
the Potential of Inhibiting GLP-1 Receptor Activity as a Targeted Approach Insulin Glucose (mg/dL, mean SEM) Proof of Concept in People ( U/mL, mean SEM) with PBH (N=8) Demonstrated: Placebo Placebo 100% prevention
of Avexitide Avexitide hypoglycemia NS-Controls NS-Controls Increased the plasma glucose nadir by 70%, matching NS controls Ameliorated hyperinsulinemia Glycemic Rescue Below 50 mg/dL Time (min) Time (min) 8 GLP-1=glucagon-like
peptide-1; NS-Controls=Non-surgical controls; PBH=post-bariatric hypoglycemia; SEM=standard error of the mean; Craig et al. Diabetologia 2017
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% 50 >50% p=0.04
40 % 23 30 p=0.2 Treatment effect 20 supported by consistent, 10 0 dose-dependent effects Avexitide 30 mg Avexitide 60 mg Avexitide 45 mg Avexitide 90 mg across Phase 1, SAD, and twice daily once a day twice daily once a day MAD trials in PBH PHASE
2B STUDY PHASE 2 PREVENT STUDY MAD=multiple ascending dose; PBH=post-bariatric hypoglycemia; SAD=single ascending dose; 1. Craig, C. M. et al. The Journal of Clinical Endocrinology & Metabolism. 2021;106(8):e3235- e3248.
doi.org/10.1210/jendso/bvac150.725; 2. Tan, M. (2022). Efficacy and Safety of Avexitide for Treatment of Hypoglycemia after Gastrointestinal Surgery: Assessment of Novel Dosing Regimens in an Expanded Indication [Conference presentation]. ENDO
Annual Symposium. 9 % Reduction in Rate of Hypoglycemia (Least Squared Mean)
Avexitide Significantly Reduced Rates of Composite Level 2 and 3 FDA
Breakthrough Hypoglycemia in New Exploratory Analysis Therapy Designation % Reduction in Rate of Hypoglycemia by Avexitide Dose % Reduction in Composite Phase 3 program will 100 a b Rate of Level 2 and evaluate 90 mg once 90 Level 2 Level 3 c daily
in people with PBH 3 Hypoglycemia 68% 66% 80 64% p=0.0003 60% p=0.0003 70 57% 56% FDA-agreed upon p=0.0031 p=0.004 53% p=0.01 p=0.003 60 primary endpoint: p=0.004 40% Reduction in the 50 p=0.04 composite of 40 % 23 Level 2 and Level 3 30 p=0.2
hypoglycemic events 20 10 All dose regimens 0 demonstrated consistent Avexitide 90 mg Avexitide 30 mg Avexitide 60 mg Avexitide 45 mg Avexitide 90 mg reductions in composite once a day twice daily once a day twice daily once a day rate of Level 2
and Level 3 hypoglycemic events EXPLORATORY ANALYSIS PHASE 2B STUDY PHASE 2 PREVENT STUDY FROM PHASE 2B STUDY FDA=U.S. Food and Drug Administration; PBH=post-bariatric hypoglycemia; 1. Craig, C. M. et al. The Journal of Clinical Endocrinology &
Metabolism. 2021;106(8):e3235-e3248. ENDO 2025 doi.org/10.1210/jendso/bvac150.725. 2. Tan, M. (2022). Efficacy and Safety of Avexitide for Treatment of Hypoglycemia after Gastrointestinal Surgery: Assessment of Novel Dosing PRESENTATION Regimens in
an Expanded Indication [Conference presentation]. a b ENDO Annual Symposium. Rate defined the weekly number of discrete events during respective treatment periods; Level 2 hypoglycemia: self-monitoring of blood glucose <54 c mg/dL Level 3
hypoglycemia: a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery whether an individual receives external assistance or not. 10 % Reduction in Rate of Hypoglycemia
(Least Squared Mean)
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 injection SC
injection SC injection (n=8) (N=8) 5 5 (n=5) (N=17) (N=17) Improvement vs. Placebo Postprandial Increase Increase Increase Increase Increase Glucose Nadir (p<0.001) (p<0.001) (p<0.05) (p=0.001) (p=0.0002) BID=twice daily; IV=intravenous;
MAD=multiple ascending dose; PBH=post-bariatric hypoglycemia; QD=once daily; SAD=single ascending dose; SC=subcutaneous; 1. Craig, C. M. et al. Diabetologia. 2017;60(3):531-540. doi:10.1007/s00125-016-4179-x; 2. Craig, C. M. et al. Diabetes, Obesity
& Metabolism. 2018;20:352-361. doi.org/10.1111/dom.13078; 3. Tan, M. et al. Diabetes, Obesity & Metabolism. 2020;22(8):1406-1416. doi:10.1111/dom.14048; 4. Craig, C. M. et al. The Journal of Clinical Endocrinology & Metabolism.
2021;106(8):e3235-e3248. doi:10.1210/clinem/dgab103; 5.18 participants were randomized and completed the trial with 17 included in the efficacy analysis due to a major protocol deviation (glycemic rescue 11 was not administered as indicated per
protocol during the Period 1 placebo MMTT).
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-related serious AEs
1 serious adverse event (presyncope fasting or peak postprandial during avexitide 60 mg once daily) No serious AEs plasma glucose levels occurred; reported as unrelated to study (i.e., no hyperglycemia drug and self-limited observed) Most
common AEs were diarrhea, Most common AEs were injection* site headache, bloating, and injection* site bruising, headache, and nausea reaction/bruising No participant discontinuations No participant discontinuations *Injection site reactions
generally mild and transient with no grade 3 events or resulting discontinuations AE=adverse event; 1. Craig, C. M. et al. The Journal of Clinical Endocrinology & Metabolism. 2021;106(8):e3235-e3248. doi.org/10.1210/jendso/bvac150.725. 2. Tan,
M. (2022). Efficacy and Safety of Avexitide for Treatment of Hypoglycemia after Gastrointestinal Surgery: Assessment of Novel Dosing Regimens in an Expanded Indication [Conference presentation]. ENDO Annual Symposium. 12
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 Participants
enrolled 1:1 Placebo Avexitide 30 mg BID Avexitide 60 mg QD Randomization 14-day Eligibility had Roux-en-Y gastric bypass (RYGB) Run-in Period Placebo Avexitide 60 mg QD Avexitide 30 mg BID At least 2 hypoglycemic events during 14-day run-in period
despite adhering to consistent dietary management MMTT MMTT MMTT PHASE 2B TRIAL DESIGN - 28-day, open-label, investigator-initiated, crossover trial (N=16) 14-day Treatment Period 14-day Treatment Period Participants enrolled had RYGB, 1:1 Avexitide
90 mg QD Avexitide 45 mg BID 14-day Eligibility Randomization vertical sleeve gastrectomy, Run-in Period esophagectomy, Nissen Avexitide 45 mg BID Avexitide 90 mg QD fundoplication, or gastrectomy At least 2 hypoglycemic events during 14-day run-in
period 2-day washout despite adhering to consistent dietary management PHASE 3 LUCIDITY TRIAL DESIGN - Multicenter, randomized, double-blind, placebo-controlled trial (N=~75) 16-week Double-blind Treatment Period 32-week Treatment Period 3:2
Avexitide 90 mg QD 21-day Eligibility Randomization Participants to be enrolled Open-label Extension (OLE) Run-in Period will have had RYGB Placebo At least 3 hypoglycemic events during 21-day run-in period despite adhering to consistent dietary
management BID=twice daily; MMTT=mixed meal tolerance testing; PBH=post-bariatric hypoglycemia; QD=once daily. 13
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, Gastrectomy
Hypoglycemic events despite Hypoglycemic events despite Hypoglycemic events despite Study Population: dietary management dietary management dietary management Diet Run-In Hypoglycemic At least one per week At least one per week At least one per week
Event Rate 30 mg BID/60 mg QD 45 mg BID/90 mg QD 90 mg QD (90 mg QD administered as 2 sequential (90 mg QD administered as 2 sequential Avexitide Dose injections) injections during double blind treatment period and OLE Part A and as 1 injection
during OLE Part B) Exploratory: Secondary: Primary: Endpoints Level 2 hypoglycemic events Level 2 hypoglycemic events Composite of Level 2 and Level Level 3 hypoglycemic events Level 3 hypoglycemic events 3 hypoglycemic events 14 BID=twice daily;
PBH=post-bariatric hypoglycemia; QD=once daily; RYGB=Roux-en-Y gastric bypass; OLE=open-label extension.
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 Currently living
with speaking, blurred vision 1-3 PBH in the U.S. PBH develops on average 1-3 years Risk of falls, seizures, vehicle accidents No approved treatment options post surgery Job and income loss Rate of Gastric Bypass by Type 350,000
300,000 LIVING WITH PBH 250,000 BETWEEN 2013-2023 200,000 "It affected my ability to work and Sleeve.....~1.4 million 150,000 take care of my family." RYGB......~0.6 Million 100,000 Total ~2.5 Million "I pass
out multiple times a week. 50,000 0 My lows are averaging 4-5 times 2013 '14 '15 '16 '17 '18 '19 '20 '21 22 2023 a day." Sleeve RYGB Total "I lost my driver's license since I am unaware of my lows." PBH=post-bariatric
hypoglycemia; RYGB=Roux-en-Y gastric bypass; 1. Estimate of Bariatric Surgery Numbers, 2013-2023. American Society for Metabolic and Bariatric Surgery (ASMBS). Accessed May 8, 2025. 2. Raverdy V. et al. Annals of Surgery. 2016;264(5):878-885.
doi:10.1097/SLA.0000000000001768. 3. de Heide, L. J. M. et al. Diabetes, Obesity, & Metabolism. 2023;25:735-747. doi.org/10.1111/dom.14920. 15
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 and 54.3% in those
examining SG 3 Prospective, Longitudinal Cohort (N=1,448) 43.2% prevalence of post-RYGB hypoglycemia symptoms ~2 Million from 2013-2023 Total U.S. Bariatric Surgeries 32.8% of participants had at least one OGTT-related hypoglycemia 4 Prospective
1-Year Study (N=186) after laparoscopic sleeve gastrectomy 32.6% showed post-challenge hypoglycemia after RYGB; 5 Prospective 2-Year Study (N=281) ~20- 22.6% after SG Prevalence of Hypoglycemia ~400K - 1M 50% 6 Retrospective Survey (N=341) 29%
with new-onset hypoglycemia symptoms post-RYGB or SG Following Bariatric Surgery Of 107 individuals with PBH treated with acarbose, 37% had 7 persistent/unacceptable frequency of hypoglycemic events Retrospective Study (N=120) b [Note: Equates to