Amylyx Pharmaceuticals (AMLX) investor relations material

Avexitide mechanism and clinical need

• Avexitide is a first-in-class GLP-1 receptor antagonist that lowers insulin and raises blood glucose, targeting hyperinsulinemic hypoglycemia, particularly post-bariatric hypoglycemia (PBH).

• PBH affects about 160,000 people in the U.S., causing severe neurological complications due to frequent hypoglycemic events, with no approved treatments currently available.

• Current management relies on medical nutrition therapy, but patients continue to experience severe events due to GLP-1 overproduction.

Clinical trial data and study design

• Five prior trials of avexitide in PBH showed significant reductions in hypoglycemic events, supporting FDA breakthrough therapy designation.

• The pivotal phase III LUCIDITY trial is fully enrolled, with top-line results expected in Q3; it uses a 16-week randomized placebo-controlled design with an open-label extension.

• The primary endpoint is reduction in level II (blood glucose <54 mg/dL) and level III (requiring independent rescue) hypoglycemic events, consistent with prior studies.

• Prior phase II-B data showed a 64% reduction in severe hypoglycemic events at the highest dose, with a p-value of 0.003.

• Placebo effect in PBH trials has been negligible, as patients continue to experience events despite all efforts.

Market opportunity and future plans

• PBH is a large orphan population, with about 120,000 of 160,000 U.S. cases linked to Roux-en-Y gastric bypass.

• Centers of excellence and large endocrinology clinics manage significant numbers of PBH patients, confirming the market size.

• If approved, avexitide’s initial label may focus on Roux-en-Y PBH, but expansion to other surgery-induced hypoglycemias is anticipated.

• Additional indications are being explored, including hypoglycemia after other GI surgeries and a long-acting GLP-1 antagonist (AMX0318) is in IND-enabling studies, aiming for clinical trials next year.

• Cash runway extends into 2028, including a planned avexitide launch in 2027.