Amylyx Pharmaceuticals, Inc. Q4 FY2024 earnings call

• Key milestones across 3 assets in 4 ongoing clinical trials targeting orphan diseases. • Pivotal study of avexitide for post-bariatric hypoglycemia with top line results expected in first half of 2026; started recruiting LUCIDITY trial. • AMX0035 in Wolfram syndrome (HELIOS trial ongoing, week 48 data expected) and progressive supranuclear palsy (ORION trial, unblinded interim analysis in third quarter 2025). • AMX0114 in ALS (Phase I LUMINA trial recruiting, early cohort data expected later in 2025). • Completed financing raising ~$65.5 million for avexitide commercial preparations and cash runway extension. • Cash position at end of 2024 was $176.5 million, with cash runway through end of 2026.

No detailed financial performance breakdown by product segments provided in terms of absolute revenue and contribution %

• Avexitide's pivotal Phase III LUCIDITY trial top line data expected in first half of 2026. • Week 48 data from HELIOS trial in Wolfram syndrome expected. • Unblinded interim analysis of ORION trial in PSP (Phase IIb portion) in third quarter 2025. • Data from Phase I LUMINA trial of AMX0114 in ALS expected later in 2025. • Commercial preparations for potential first-to-market launch of avexitide in post-bariatric hypoglycemia.

Q: Why limit the entry criteria to just Roux-en-Y gastric bypass procedures and not include sleeve gastrectomy in the PBH Phase III?

A: Camille Bedrosian stated they have the most experience with avexitide in people who've had Roux-en-Y and developed PBH, but recognize pathophysiology is consistent across bariatric surgeries, with intention to expand later.

Q: Could you remind us how efficacy will be interpreted in the PSP ORION study across regions given the use of the 10-item PSP rating scale in the U.S. as a primary and the 28-item PSP rating scale in ex-U.S. jurisdictions?

A: Joshua Cohen noted that different regulators have different rating scale preferences, but experience shows results from both scales are likely very similar.

Q: What is the target profile that you guys are looking to achieve with the long-acting GLP-1? And how does this profile compare to other long-acting GLP-1s like Amgen's MariTide and Metsera's MET-097i?

A: Justin Klee explained avexitide is a GLP-1 antagonist, unlike agonists like MariTide and MET-097i, and they're excited about its mechanism for potential future applications.

Q: How are you guys forecasting future patient numbers for PBH? I guess I'm just trying to understand, I think the market will shrink, right, over time, given current use of GLP-1s, which would mean that fewer patients probably get bariatric surgery.

A: Joshua Cohen and Justin Klee stated the market will continue to grow as PBH is persistent, with ongoing bariatric surgery demand and PBH not going away once developed.

Q: For the Wolfram syndrome trial, could you discuss what you're looking for in the week 48 data that will help inform regulatory interactions?

A: Camille Bedrosian mentioned looking for continued sustained improvements in C-peptide response, hypoglycemic control measures, and potential stabilization/improvement in visual acuity.

Q: Can you discuss the potential to develop avexitide for other indications beyond PBH?

A: Joshua Cohen stated focus is on PBH initially, but believe mechanism could be important for other hyperinsulinemic hypoglycemia and related diseases.

Q: We've heard from some physicians that there are some patients who exhibit PBH without the postprandial hyperinsulinism. So we're curious if you're screening for patients who specifically show a spike in insulin levels post meal. Has your research shown like a specific proportion of patients who show this in PBH?

A: Joshua Cohen said inclusion/exclusion criteria are similar to previous trials where large effect size and high statistical significance were seen, and they're well-positioned for the Phase III study.

Q: How should we be thinking of the pricing for avexitide? We know it's early, but just wanted to get like a ballpark idea.

A: Joshua Cohen said too early for definitive pricing, but encouraged looking at orphan drug analogs and efficacy's impact on pricing.