Amylyx Pharmaceuticals, Inc. Q3 FY2024 earnings call

• Progressed lead asset avexitide, a GLP-1 receptor antagonist with FDA breakthrough and orphan drug designations, on track for Phase III trial in PBH Q1 2025. • Positive topline data from Phase II HELIOS trial of AMX0035 in Wolfram syndrome, showing improvement in pancreatic function and other endpoints, planning Phase III meeting with FDA. • ORION-PSP trial of AMX0035 in PSP recruiting well, interim analysis expected mid-2025. • Received Health Canada clearance for AMX0114 Phase I trial in ALS, plan to start in Canada, submitted INDA to FDA but faced clinical hold, working to address FDA comments. • Strong financial position with cash runway into 2026, expecting combined R&D and SG&A spend $30-40M per quarter excluding stock-based comp.

Net product revenues for the third quarter were $400,000 with cost of sales at $800,000. Research and development expenses were $21.2 million, selling, general and administrative expenses were $17.8 million. The company recorded a net loss of $72.7 million or $1.07 per share. Cash and investments at the end of Q3 were $234.4 million.

• On track to initiate Phase III trial in post-bariatric hypoglycemia (PBH) in Q1 2025. • Plan to meet with FDA and stakeholders on Phase III program for Wolfram syndrome, expect update in 2025. • ORION-PSP trial interim analysis mid-2025 to inform go/no-go decision. • Plan to begin Phase I AMX0114 trial in ALS in Canada in coming months, expect early cohort data in 2025. • Cash runway expected to take company into 2026.

• Actual events and results could differ materially from forward-looking statements. • FDA comments on AMX0114 trial starting dose led to clinical hold, need to address FDA concerns. • Uncertainties in clinical trial outcomes for various programs, including the success of Phase III trials and interim analyses.

Q: How should we think about the market size for PBH patients that are efficaciously managed by existing therapy? And what are the gating factors to initiating the Phase III PBH study?

A: James Frates said estimated 160,000 people with PBH, Camille Bedrosian said on track to initiate trial Q1 2025 with clinical sites and team working well Q: Given what we know about the Eiger, previous agreement with the FDA on this trial design, what are the other factors, like how you are contemplating with in terms of design? And is there a potential to have readout earlier in 2026?

A: Camille Bedrosian said working with FDA on trial design, refining around edges, primary endpoint composite Level 2 and Level 3 hypoglycemia, study to begin Q1 2025, data in 2026 Q: On avexitide, how do you think about the risk of hyperglycemia since the GLP-1 antagonists don't address this happening? And with regard to AMX0114, any color on why the FDA deemed the 12.5 milligram dose to be too high?

A: Camille Bedrosian said avexitide not anticipated to cause hyperglycemia, well-tolerated; Justin Klee added side effects are injectable peptide typical. For AMX0114, FDA has questions, independent toxicologists see 12.5mg 10x below NOAEL, working to address FDA comments Q: On the ORION study, can we have more on biomarker data? And regarding the Phase III avexitide, are you planning to include an active arm with standard of care?

A: Camille Bedrosian said PSP study primarily looking at CSF biomarker data; Camille Bedrosian said Phase III avexitide trial will be placebo vs no active standard of care as none approved for PBH Q: On avexitide pharmacokinetic profile for 90-milligram dose with respect to hypoglycemic events?

A: Joshua Cohen said avexitide reaches therapeutic range ~1 hour post dosing, remains in range ~24 hours, PK/PD modeling shows quick onset of effect Q: How do you think about balancing remaining cash among lead program, other programs, and potential business development?

A: James Frates said view avexitide as lead asset, other programs have important milestones, cash runway to get through Phase III data on avexitide, will manage cash accordingly