Amylyx Pharmaceuticals (AMLX) investor relations material

Pipeline overview and clinical programs

• Three ongoing clinical programs: Avexetide (lead), a small molecule for Wolfram syndrome, and AMX114 for ALS.

• Avexetide is in a pivotal phase 3 trial for post-bariatric hypoglycemia (PBH), with enrollment completion expected in Q1 and top-line results in Q3 next year.

• Wolfram syndrome program had positive phase II results; phase 3 trial planned for the second half of next year pending FDA alignment.

• AMX114 is in a multiple ascending dose study for ALS, with early cohort data expected later this year and biomarker data in the first half of next year.

• Focus remains on Avexetide due to its pivotal status and significant unmet need in PBH.

Market opportunity and unmet need in PBH

• PBH is a rare but severe complication post-bariatric surgery, affecting an estimated 160,000 people in the U.S.

• 8% of bariatric surgery patients may develop PBH, with 120,000 cases from Roux-en-Y gastric bypass and 40,000 from sleeve gastrectomy.

• PBH leads to severe hypoglycemia, causing neuroglycopenia and frequent medical emergencies.

• No FDA-approved treatments exist for PBH, and the treating community is increasingly recognizing the condition.

• Patient feedback highlights significant disability and life disruption due to PBH.

Clinical trial design and regulatory progress

• Avexetide phase 3 trial closely replicates successful phase II design, with stricter run-in criteria and a longer 16-week dosing period.

• Primary endpoint is a composite of level two and level three hypoglycemia events, with strong prior data showing significant reductions.

• Study is 90% powered to detect a 35% therapeutic effect, with phase IIB showing a 64% effect.

• Dietary adherence is managed through training and attestation at each visit to minimize confounding.

• FDA engagement has been strong, with breakthrough therapy designation and protocol alignment.