Amylyx Pharmaceuticals Announces Acquisition of Phase 3-ready GLP-1 Receptor Antagonist (Avexitide) with FDA Breakthrough Therapy Designation

- Avexitide is a novel, first-in-class GLP-1 receptor antagonist with the potential to treat hyperinsulinemic hypoglycemia

- FDA Breakthrough Therapy Designation granted for avexitide for post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism

- Acquisition builds on Amylyx’ endocrine and neuroscience expertise and aligns with pipeline focus of delivering important potential treatment options to communities with high unmet needs

- Phase 3 program for avexitide in PBH expected to begin in Q1 2025, with data readout anticipated in 2026; FDA has agreed to the primary endpoint expected to be utilized in Phase 3

- Data from two Phase 2 studies of avexitide in people with PBH demonstrated highly statistically significant reductions in severe hypoglycemic events, an endpoint supported by the FDA

- Avexitide was generally well tolerated, with a favorable safety profile replicated across five clinical trials in people with PBH

- Management to host conference call and webcast today at 8:00 a.m. Eastern Time

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced the acquisition of avexitide from Eiger BioPharmaceuticals, Inc. (“Eiger”). Avexitide has been studied for the potential treatment of hyperinsulinemic hypoglycemia to date.

“Since Amylyx was founded, we have been guided by a rigorous approach to our science to bring potential treatments to communities with high unmet needs. When we reviewed all the compelling data supporting avexitide, it clearly aligned with our strategic scientific criteria, expertise, and community values, and we are excited to build upon the important work done to date to study this asset,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx.

Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five clinical trials for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI), two indications characterized by hyperinsulinemic hypoglycemia. The U.S. Food and Drug Administration (FDA) has granted avexitide Breakthrough Therapy Designation for both indications, Rare Pediatric Disease Designation in congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia (which includes PBH and congenital HI).

Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and block the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels. In PBH, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent severe hypoglycemic events, including autonomic and neuroglycopenic symptoms if left unaddressed.

In previous Phase 2 and Phase 2b studies in PBH, avexitide showed statistically significant reductions in hypoglycemic events characterized by low blood glucose, including severe hypoglycemic events with altered mental and/or physical function requiring assistance. FDA guidance for industry combined with initial FDA feedback specific to the pivotal Phase 3 program of avexitide for PBH suggest that reduction in hypoglycemia events could be an endpoint to support approval following positive results from a pivotal Phase 3 clinical trial.

Amylyx expects to begin the Phase 3 program for avexitide in PBH in Q1 2025. Furthermore, Amylyx is actively engaging in discussions with the broader congenital HI community, including experts in the field, to develop a path forward based on promising Phase 2 study results conducted at Children's Hospital of Philadelphia. Avexitide will be added to Amylyx’ current pipeline programs that have been in research and development for several years: AMX0035 for the treatment of Wolfram syndrome, AMX0035 for the treatment of progressive supranuclear palsy, and AMX0114, the Company’s antisense oligonucleotide targeting calpain-2 for the treatment of amyotrophic lateral sclerosis, or ALS.

Avexitide in PBH: Key Clinical Trial Results to Date

The following table shows key results from the Phase 2, randomized, placebo-controlled crossover study (PREVENT) that evaluated efficacy and safety of avexitide for treatment of PBH following Roux-en-Y gastric bypass surgery. The results showed that, compared with placebo, avexitide 30 mg twice daily (BID) and 60 mg once daily (QD) significantly increased mean plasma glucose nadir (prespecified primary endpoint) and lowered insulin peak, corresponding to 50% and 75% fewer participants requiring rescue during mixed meal tolerance testing, respectively. Significant reductions in rates of Levels 1, 2, and 3 hypoglycemia were observed. Continuous glucose monitoring (CGM) demonstrated reductions in time in hypoglycemia without induction of clinically relevant hyperglycemia.