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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
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's program development activities, including ongoing and planned clinical trials, Amylyx's ability to execute on its development and regulatory strategy, regulatory developments, Amylyx's cash
runway and ability to fund operations, as well as the risks and uncertainties set forth in Amylyx's United States Securities and Exchange Commission (SEC) filings, including Amylyx's Annual Report on Form 10-K for the year ended December
31, 2025, 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. Enrollment completed. Topline
Post-Bariatric AVEXITIDE data expected in Q3 2026, and if approved, commercial launch Hypoglycemia LUCIDITY PHASE 3 CLINICAL TRIAL anticipated in 2027 GLP-1 receptor (PBH) antagonist FDA-agreed upon primary outcome of reduction in the
composite of Level 2 and Level 3 hypoglycemic events through Week 16 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 Completed enrollment in Cohort 2
(n=12) in March 2026 (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 PBH and
Other in vivo efficacy and tolerability, high solubility, and a favorable Long-acting GLP-1 Rare Diseases pharmacokinetic profile consistent with a long-acting peptide receptor antagonist IND-enabling studies underway, with an IND filing
targeted for 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 GLP-1 Receptor Antagonist with
FDA Breakthrough Therapy Designation Pancreatic islet cells
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 Level 2
and Level 3 hypoglycemic events in PBH following RYGB surgery Topline data from > Completed enrollment in LUCIDITY in March 2026 Q3 2026 avexitide Phase 3 trial in PBH Prior clinical studies generated highly statistically significant
reductions in hypoglycemic events Commercial launch of PBH is an orphan condition that is often life-altering; avexitide in 2027, if 2027 ~160,000 prevalent patients approved Strong IP position with patent rights through 2037 and
potential for patent term extension 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 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 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 GLP-1 Receptor Antagonism 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 Squares Mean)
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 Level 3 c daily in
people with PBH 3 Hypoglycemia 68% 66% 80 64% p=0.0003 60% p=0.0003 70 57% FDA-agreed upon 56% 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 Squares Mean)
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 Placebo 2 (28 days) (14
days) Twice Daily Daily n=17 n=17 n=17 n=17 n=17 LUCIDITY model for Primary endpoint analysis (negative binomial regression) Composite Weekly Rate of Level 2&3 Hypoglycemia applied to PREVENT and Phase 2b Mean (SD) 1.37 (1.244) 2.19
(2.144) 1.47 (1.049) 0.89 (1.101) 0.66 (0.609) datasets demonstrates significant Median 1.04 1.50 1.50 0.50 0.50 reduction in composite of Level 2 and 3 Rate Ratio (over placebo of hypoglycemia during treatment period) Level 3 hypoglycemia LS Mean
(SE) N/A N/A N/A 0.61 (0.245) 0.45 (0.224) 90 mg once daily dose reduced weekly 95% CI N/A N/A N/A 0.374, 1.003 0.288, 0.709 events from 1.39 to 0.59 (mean) and 0.93 P-Value N/A N/A N/A 0.0514 0.0009 to 0 (median) compared with run-in
90 mg once daily dose led to highly Table 2. Reduced Rates of Composite Level 2 and 3 Hypoglycemia in Phase 2b Study statistically 64% reduction in composite Run-In Period Avexitide 45 mg Twice Daily Avexitide 90 mg Daily events (p=0.0031)
N=16 N=16 N=16 Composite Weekly Rate of Level 2&3 Hypoglycemia LUCIDITY trial is estimated to be 90% 1.39 (1.908) 0.51 (0.719) 0.59 (1.604) Mean (SD) powered to detect a 35% relative 0.93 0.25 0 Median improvement over placebo
even with up Rate Ratio (over run-in of hypoglycemia during treatment period) to a 50% placebo effect N/A 0.38 (0.298) 0.36 (0.325) LS Mean (SE) N/A 0.206, 0.687 0.187, 0.694 95% CI N/A 0.0021 0.0031 P-Value 1. Table 1 is updated from Poster SUN-627
at ENDO 2025 Annual Meeting ( ENDO Poster ). 2. ENDO Poster displayed this information as Run-in Period. The values represented event rate normalized to the 28-day Screening Period, including the 14-day Eligibility Run-In Period. 3. Updated model
from ENDO Poster utilizing 14-day Run-In Period instead of the 28-day Screening Period for the run-in event rate covariate. 11
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 12 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. 13
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=78) 16-week Double-blind Treatment Period 32-week Treatment Period 3:2
Avexitide 90 mg QD Enrollment complete. 21-day Eligibility Randomization Open-label Extension (OLE) Participants enrolled have RYGB Run-in Period 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. 14
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 15 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